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Jung JH, Kang SA, Park JH, Kim SD, Yu HS, Mun SJ, Cho KS. Paraoxonase-1 Is a Pivotal Regulator Responsible for Suppressing Allergic Airway Inflammation Through Adipose Stem Cell-Derived Extracellular Vesicles. Int J Mol Sci 2024; 25:12756. [PMID: 39684469 DOI: 10.3390/ijms252312756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 11/20/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
Although adipose stem cell (ASC)-derived extracellular vesicles (EVs) are as effective as ASCs in the suppression of Th2 cell-mediated eosinophilic inflammation, the role of identified pulmonary genes has not been well documented. Thus, we assessed the immunomodulatory effects of paraoxonase-1 (PON1) on allergic airway inflammation in a mouse model of asthma. Five-week-old female C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of PON1 on allergic airway inflammation, the intranasal and intraperitoneal injections of recombinant mouse serum PON1 (5 μg/50 μL) were performed before the OVA challenge. We evaluated airway hyperresponsiveness (AHR), total inflammatory cells, and eosinophils in the bronchoalveolar lavage fluid (BALF), lung histology, serum immunoglobulin (Ig), cytokine profiles of BALF and lung draining lymph nodes (LLNs), the expression of interleukin (IL)-25 and transforming growth factor (TGF)-β in mouse lung epithelial cell (MLE-12 cell), and dendritic cell (DC) differentiation. The intraperitoneal and intranasal administration of PON1 significantly decreased AHR, total inflammatory cells and eosinophils in BALF, eosinophilic airway inflammation, serum total, and OVA-specific IgE. PON1 treatment, which marked reduced IL-4, IL-5, and IL-13 in the BALF and LLN but significantly increased interferon-γ and TGF-β. Furthermore, PON1 treatment significantly decreased the expression of IL-25 and increased TGF-β in MLE-12 cells. The expressions of CD40, CD80, and CD86 in immature DCs were significantly increased by PON1 treatment. The administration of PON1 ameliorated allergic airway inflammation and improved AHR through the downregulation of IL-4, IL-5, and IL-13 and upregulation of TGF-β in asthmatic mice. Furthermore, PON1 treatment decreased Th2-mediated inflammation induced by Aspergillus protease antigen by decreasing IL-25 and increasing TGF-β.
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Affiliation(s)
- Jae Hoon Jung
- Department of Otorhinolaryngology, Pusan National University School of Medicine, Busan 50612, Republic of Korea
| | - Shin Ae Kang
- Department of Environmental Medical Biology, Catholic Kwandong University College of Medicine, Gangneung 25601, Republic of Korea
| | - Ji-Hwan Park
- Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, Busan 50612, Republic of Korea
| | - Sung-Dong Kim
- Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, Busan 50612, Republic of Korea
| | - Hak Sun Yu
- Department of Parasitology and Tropical Medicine, Pusan National University School of Medicine, Busan 50612, Republic of Korea
| | - Sue Jean Mun
- Department of Otorhinolaryngology and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Busan 50612, Republic of Korea
| | - Kyu-Sup Cho
- Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, Busan 50612, Republic of Korea
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Zinellu A, Mangoni AA. The potential role of serum amyloid A as biomarker of rheumatic diseases: a systematic review and meta-analysis. Clin Exp Med 2024; 24:141. [PMID: 38951267 PMCID: PMC11217051 DOI: 10.1007/s10238-024-01413-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 06/19/2024] [Indexed: 07/03/2024]
Abstract
The identification of novel, robust biomarkers for the diagnosis of rheumatic diseases (RDs) and the presence of active disease might facilitate early treatment and the achievement of favourable long-term outcomes. We conducted a systematic review and meta-analysis of studies investigating the acute phase reactant, serum amyloid A (SAA), in RD patients and healthy controls to appraise its potential as diagnostic biomarker. We searched PubMed, Scopus, and Web of Science from inception to 10 April 2024 for relevant studies. We evaluated the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively (PROSPERO registration number: CRD42024537418). In 32 studies selected for analysis, SAA concentrations were significantly higher in RD patients compared to controls (SMD = 1.61, 95% CI 1.24-1.98, p < 0.001) and in RD patients with active disease compared to those in remission (SMD = 2.17, 95% CI 1.21-3.13, p < 0.001). Summary receiving characteristics curve analysis showed a good diagnostic accuracy of SAA for the presence of RDs (area under the curve = 0.81, 95% CI 0.78-0.84). The effect size of the differences in SAA concentrations between RD patients and controls was significantly associated with sex, body mass index, type of RD, and study country. Pending the conduct of prospective studies in different types of RDs, the results of this systematic review and meta-analysis suggest that SAA is a promising biomarker for the diagnosis of RDs and active disease.
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Affiliation(s)
- Angelo Zinellu
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Arduino A Mangoni
- Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, Adelaide, SA, 5042, Australia.
- Department of Clinical Pharmacology, Flinders Medical Centre, Southern Adelaide Local Health Network, Adelaide, Australia.
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Yan J, Yang S, Han L, Ba X, Shen P, Lin W, Li T, Zhang R, Huang Y, Huang Y, Qin K, Wang Y, Tu S, Chen Z. Dyslipidemia in rheumatoid arthritis: the possible mechanisms. Front Immunol 2023; 14:1254753. [PMID: 37954591 PMCID: PMC10634280 DOI: 10.3389/fimmu.2023.1254753] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 10/09/2023] [Indexed: 11/14/2023] Open
Abstract
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, of which the leading cause of death is cardiovascular disease (CVD). The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) in RA decrease especially under hyperinflammatory conditions. It is conflictive with the increased risk of CVD in RA, which is called "lipid paradox". The systemic inflammation may explain this apparent contradiction. The increased systemic proinflammatory cytokines in RA mainly include interleukin-6(IL-6)、interleukin-1(IL-1)and tumor necrosis factor alpha(TNF-α). The inflammation of RA cause changes in the subcomponents and structure of HDL particles, leading to a weakened anti-atherosclerosis function and promoting LDL oxidation and plaque formation. Dysfunctional HDL can further worsen the abnormalities of LDL metabolism, increasing the risk of cardiovascular disease. However, the specific mechanisms underlying lipid changes in RA and increased CVD risk remain unclear. Therefore, this article comprehensively integrates the latest existing literature to describe the unique lipid profile of RA, explore the mechanisms of lipid changes, and investigate the impact of lipid changes on cardiovascular disease.
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Affiliation(s)
- Jiahui Yan
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Sisi Yang
- Department of Geriatrics, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Liang Han
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Xin Ba
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Pan Shen
- Department of Rheumatology and Immunology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Weiji Lin
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Tingting Li
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Ruiyuan Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Ying Huang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Yao Huang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Kai Qin
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Yu Wang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Shenghao Tu
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Zhe Chen
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
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Ronda N, Zimetti F, Adorni MP, Palumbo M, Karpouzas GA, Bernini F. Role of Lipoprotein Levels and Function in Atherosclerosis Associated with Autoimmune Rheumatic Diseases. Rheum Dis Clin North Am 2023; 49:151-163. [PMID: 36424022 DOI: 10.1016/j.rdc.2022.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Immune and inflammatory mediators in autoimmune rheumatic diseases induce modification in the activity of enzymes pivotal for lipid metabolism and promote a proatherogenic serum lipid profile. However, disturbances in low- and high-density lipoprotein composition and increased lipid oxidation also occur. Therefore, lipoprotein dysfunction causes intracellular cholesterol accumulation in macrophages, smooth muscle cells, and platelets. Overall, both plaque progression and acute cardiovascular events are promoted. Single rheumatic diseases may present a particular pattern of lipid disturbances so that standard methods to evaluate cardiovascular risk may not be accurate enough. In general, antirheumatic drugs positively affect lipid metabolism in these patients.
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Affiliation(s)
- Nicoletta Ronda
- Department of Food and Drug, University of Parma, Parco Area delle Scienze, 27/A, Parma 43124, Italy.
| | - Francesca Zimetti
- Department of Food and Drug, University of Parma, Parco Area delle Scienze, 27/A, Parma 43124, Italy
| | - Maria Pia Adorni
- Department of Medicine and Surgery, Unit of Neuroscience, University of Parma, Via Volturno 39/F, Parma 43125, Italy
| | - Marcella Palumbo
- Department of Food and Drug, University of Parma, Parco Area delle Scienze, 27/A, Parma 43124, Italy
| | - George A Karpouzas
- Division of Rheumatology, Harbor-UCLA Medical Center and the Lundquist Institute, Torrance, CA, USA
| | - Franco Bernini
- Department of Food and Drug, University of Parma, Parco Area delle Scienze, 27/A, Parma 43124, Italy
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Kim SD, Cho KS. Immunomodulatory Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Allergic Airway Disease. LIFE (BASEL, SWITZERLAND) 2022; 12:life12121994. [PMID: 36556359 PMCID: PMC9786036 DOI: 10.3390/life12121994] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/23/2022] [Accepted: 11/25/2022] [Indexed: 12/03/2022]
Abstract
Mesenchymal stem cells (MSCs) have been reported as promising candidates for the treatment of various diseases, especially allergic diseases, as they have the capacity to differentiate into various cells. However, MSCs itself have several limitations such as creating a risk of aneuploidy, difficulty in handling them, immune rejection, and tumorigenicity, so interest in the extracellular vesicles (EVs) released from MSCs are increasing, and many studies have been reported. Previous studies have shown that extracellular vesicles (EVs) produced by MSCs are as effective as the MSCs themselves in suppression of allergic airway inflammation through the suppression of Th2 cytokine production and the induction of regulatory T cells (Treg) expansion. EVs are one of the substances secreted by paracrine induction from MSCs, and because it exerts its effect by delivering contents such as mRNA, microRNA, and proteins to the receptor cell, it can reduce the problems or risks related to stem cell therapy. This article reviews the immunomodulatory properties of MSCs-derived EVs and their therapeutic implications for allergic airway disease.
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Affiliation(s)
- Sung-Dong Kim
- Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-Ro, Seo-gu, Busan 602-739, Republic of Korea
| | - Kyu-Sup Cho
- Department of Otorhinolaryngology and Biomedical Research Institute, Pusan National University School of Medicine, Pusan National University Hospital, 179 Gudeok-Ro, Seo-gu, Busan 602-739, Republic of Korea
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Erre GL, Bassu S, Giordo R, Mangoni AA, Carru C, Pintus G, Zinellu A. Association between Paraoxonase/Arylesterase Activity of Serum PON-1 Enzyme and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Antioxidants (Basel) 2022; 11:antiox11122317. [PMID: 36552525 PMCID: PMC9774899 DOI: 10.3390/antiox11122317] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 11/14/2022] [Accepted: 11/20/2022] [Indexed: 11/25/2022] Open
Abstract
Background: A decrease in serum paraoxonase (PON-1) and arylesterase (ARE) activity has been reported in rheumatoid arthritis (RA) patients and linked to chronic inflammation and impaired antioxidant defense. Methods: A systematic review and meta-analysis were performed to critically appraise the current evidence on plasma/serum concentrations of PON-1 and ARE activity in RA patients and healthy controls. The Web of Science, PubMed, Scopus, and Google Scholar databases were searched from inception to November 2021. We used random-effects meta-analysis. The risk of bias was estimated using the Joanna Briggs Institute Critical Appraisal Checklist tool. The certainty of the evidence was assessed with GRADE. The study complied with the PRISMA statements and was registered in PROSPERO (CRD42022345380). Results: Seventeen studies reported PON-1 activity (1144 RA patients, 797 controls) and ten reported ARE activity (1367 RA patients, 1037 controls). RA patients had significantly lower PON-1 (SMD = −1.32, 95% CI −1.94 to −0.70; p < 0.001) and ARE activity (SMD = −0.91, 95% CI −1.37 to −0.46; p < 0.001). There was substantial heterogeneity (PON, I2 97%; ARE, 95.7%, p < 0.001 for both). There was no publication bias. The pooled SMD values did not significantly change after sensitivity analysis. The certainty of the evidence was very low due to the observational nature of the studies and the large heterogeneity. Conclusion: Our meta-analysis has shown that both serum PON-1 and ARE activity are significantly lower in RA patients, suggesting a deficit in antioxidant defense mechanisms in this disease.
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Affiliation(s)
- Gian Luca Erre
- Dipartimento di Medicina, Chirurgia e Farmacia, Università degli Studi di Sassari, Viale San Pietro, 8, 07100 Sassari, Italy
- Correspondence: ; Tel.: +39-079228317; Fax: +39-079216282
| | - Stefania Bassu
- Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy
| | - Roberta Giordo
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates
| | - Arduino A. Mangoni
- Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Sturt Road, Bedford Park, SA 5042, Australia
- Department of Clinical Pharmacology, Flinders Medical Centre, Southern Adelaide Local Health Network, Flinders Drive, Bedford Park, SA 5042, Australia
| | - Ciriaco Carru
- Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy
| | - Gianfranco Pintus
- Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy
| | - Angelo Zinellu
- Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy
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Vyletelová V, Nováková M, Pašková Ľ. Alterations of HDL's to piHDL's Proteome in Patients with Chronic Inflammatory Diseases, and HDL-Targeted Therapies. Pharmaceuticals (Basel) 2022; 15:1278. [PMID: 36297390 PMCID: PMC9611871 DOI: 10.3390/ph15101278] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/03/2022] [Accepted: 10/14/2022] [Indexed: 09/10/2023] Open
Abstract
Chronic inflammatory diseases, such as rheumatoid arthritis, steatohepatitis, periodontitis, chronic kidney disease, and others are associated with an increased risk of atherosclerotic cardiovascular disease, which persists even after accounting for traditional cardiac risk factors. The common factor linking these diseases to accelerated atherosclerosis is chronic systemic low-grade inflammation triggering changes in lipoprotein structure and metabolism. HDL, an independent marker of cardiovascular risk, is a lipoprotein particle with numerous important anti-atherogenic properties. Besides the essential role in reverse cholesterol transport, HDL possesses antioxidative, anti-inflammatory, antiapoptotic, and antithrombotic properties. Inflammation and inflammation-associated pathologies can cause modifications in HDL's proteome and lipidome, transforming HDL from atheroprotective into a pro-atherosclerotic lipoprotein. Therefore, a simple increase in HDL concentration in patients with inflammatory diseases has not led to the desired anti-atherogenic outcome. In this review, the functions of individual protein components of HDL, rendering them either anti-inflammatory or pro-inflammatory are described in detail. Alterations of HDL proteome (such as replacing atheroprotective proteins by pro-inflammatory proteins, or posttranslational modifications) in patients with chronic inflammatory diseases and their impact on cardiovascular health are discussed. Finally, molecular, and clinical aspects of HDL-targeted therapies, including those used in therapeutical practice, drugs in clinical trials, and experimental drugs are comprehensively summarised.
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Affiliation(s)
| | | | - Ľudmila Pašková
- Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, 83232 Bratislava, Slovakia
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Czókolyová M, Hamar A, Pusztai A, Tajti G, Végh E, Pethő Z, Bodnár N, Horváth Á, Soós B, Szamosi S, Szentpéteri A, Seres I, Harangi M, Paragh G, Kerekes G, Bodoki L, Domján A, Hodosi K, Seres T, Panyi G, Szekanecz Z, Szűcs G. Effects of One-Year Tofacitinib Therapy on Lipids and Adipokines in Association with Vascular Pathophysiology in Rheumatoid Arthritis. Biomolecules 2022; 12:1483. [PMID: 36291691 PMCID: PMC9599623 DOI: 10.3390/biom12101483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/10/2022] [Accepted: 10/11/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Cardiovascular (CV) morbidity, mortality and metabolic syndrome are associated with rheumatoid arthritis (RA). A recent trial has suggested increased risk of major CV events (MACE) upon the Janus kinase (JAK) inhibitor tofacitinib compared with anti-tumor necrosis factor α (TNF-α) therapy. In our study, we evaluated lipids and other metabolic markers in relation to vascular function and clinical markers in RA patients undergoing one-year tofacitinib therapy. Patients and methods: Thirty RA patients treated with either 5 mg or 10 mg bid tofacitinib were included in a 12-month follow-up study. Various lipids, paraoxonase (PON1), myeloperoxidase (MPO), thrombospondin-1 (TSP-1) and adipokine levels, such as adiponectin, leptin, resistin, adipsin and chemerin were determined. In order to assess flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and arterial pulse-wave velocity (PWV) ultrasonography were performed. Assessments were carried out at baseline, and 6 and 12 months after initiating treatment. Results: One-year tofacitinib therapy significantly increased TC, HDL, LDL, APOA, APOB, leptin, adipsin and TSP-1, while significantly decreasing Lp(a), chemerin, PON1 and MPO levels. TG, lipid indices (TC/HDL and LDL/HDL), adiponectin and resistin showed no significant changes. Numerous associations were found between lipids, adipokines, clinical markers and IMT, FMD and PWV (p < 0.05). Regression analysis suggested, among others, association of BMI with CRP and PWV (p < 0.05). Adipokines variably correlated with age, BMI, CRP, CCP, FMD, IMT and PWV, while MPO, PON1 and TSP-1 variably correlated with age, disease duration, BMI, RF and PWV (p < 0.05). Conclusions: JAK inhibition by tofacitinib exerts balanced effects on lipids and other metabolic markers in RA. Various correlations may exist between metabolic, clinical parameters and vascular pathophysiology during tofacitinib treatment. Complex assessment of lipids, metabolic factors together with clinical parameters and vascular pathophysiology may be utilized in clinical practice to determine and monitor the CV status of patients in relation with clinical response to JAK inhibition.
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Affiliation(s)
- Monika Czókolyová
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Attila Hamar
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Anita Pusztai
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Gábor Tajti
- Department of Biophysics and Cell Biology, University of Debrecen, 4032 Debrecen, Hungary
| | - Edit Végh
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Zsófia Pethő
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Nóra Bodnár
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Ágnes Horváth
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Boglárka Soós
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Szilvia Szamosi
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Anita Szentpéteri
- Division of Metabolic Diseases, University of Debrecen, 4032 Debrecen, Hungary
| | - Ildikó Seres
- Division of Metabolic Diseases, University of Debrecen, 4032 Debrecen, Hungary
| | - Mariann Harangi
- Division of Metabolic Diseases, University of Debrecen, 4032 Debrecen, Hungary
| | - György Paragh
- Division of Metabolic Diseases, University of Debrecen, 4032 Debrecen, Hungary
| | - György Kerekes
- Intensive Care Unit, Department of Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
| | - Levente Bodoki
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Andrea Domján
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Katalin Hodosi
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Tamás Seres
- Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - György Panyi
- Department of Biophysics and Cell Biology, University of Debrecen, 4032 Debrecen, Hungary
| | - Zoltán Szekanecz
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
| | - Gabriella Szűcs
- Department of Rheumatology, University of Debrecen, 4032 Debrecen, Hungary
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Bae SS, Shahbazian A, Wang J, Golub I, Oganesian B, Dowd T, Vayngortin B, Wang R, Elashoff D, Reddy ST, Charles-Schoeman C. Abnormal paraoxonase-1 (PON1) enzyme activity in idiopathic inflammatory myopathies. Rheumatology (Oxford) 2022; 61:2512-2523. [PMID: 34698804 PMCID: PMC9308379 DOI: 10.1093/rheumatology/keab795] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 10/21/2021] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVES Patients with idiopathic inflammatory myopathies (IIM) have severe vascular involvement, which contributes to disease morbidity and mortality. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated protein that protects the vascular endothelium from oxidative injury and damage. The current work assessed the functional and genetic determinants of PON1 activity in IIM patients. METHODS A total of 184 IIM patients and 112 healthy controls (HC) were included. PON1 enzyme activity was assessed by paraoxonase, arylesterase and lactonase assays, and the Q192R PON1 single nucleotide polymorphism (SNP) was analysed. Multivariate regression models examined associations of PON1 activity with IIM diagnosis and myositis disease outcomes. RESULTS The arylesterase and lactonase activities of PON1 were significantly lower in IIM patients compared with HC. Higher myositis disease activity, the presence of severe IIM-associated interstitial lung disease (ILD), and the presence of MDA5 or anti-synthetase antibodies were significantly associated with lower PON1 activity. The PON1 Q192R polymorphism was strongly linked to the paraoxonase activity of PON1 in IIM, and patients with the PON1 QQ genotype had better IIM disease outcomes compared with patients with the QR or RR genotypes. CONCLUSIONS The arylesterase and lactonase activities of PON1 are significantly impaired in IIM patients compared with HC, and inversely associate with IIM disease activity and the presence of severe ILD. The PON1 QQ genotype associates with more favourable disease outcomes in IIM patients. Large prospective studies are needed to further evaluate the role of PON1 and PON1 genetic polymorphisms in the development and propagation of IIM and IIM-ILD.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Srinivasa T Reddy
- Health Services Research and Cardiology, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
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10
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Härdfeldt J, Cariello M, Simonelli S, Ossoli A, Scialpi N, Piglionica M, Pasculli E, Noia A, Berardi E, Suppressa P, Piazzolla G, Sabbà C, Calabresi L, Moschetta A. Abdominal obesity negatively influences key metrics of reverse cholesterol transport. Biochim Biophys Acta Mol Cell Biol Lipids 2022; 1867:159087. [PMID: 34813947 DOI: 10.1016/j.bbalip.2021.159087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 11/09/2021] [Accepted: 11/14/2021] [Indexed: 12/26/2022]
Abstract
Cardiometabolic risk factors increase the risk of atherosclerotic cardiovascular disease (ASCVD), but whether these metabolic anomalies affect the anti-atherogenic function of reverse cholesterol transport (RCT) is not yet clearly known. The present study aimed to delineate if the function and maturation of high density lipoprotein (HDL) particles cross-sectionally associate with surrogate markers of ASCVD in a population comprising of different degree of cardiometabolic risk. We enrolled 131 subjects and characterized cardiometabolic risk based on the IDF criteria's for metabolic syndrome (MS). In this population, cholesterol efflux capacity (CEC), Lecithin-cholesterol acyltransferase (LCAT) and ApoA-1 glycation was associated with waist circumference, abdominal visceral fat (VFA) and abdominal subcutaneous fat. In multivariate analyses, VFA was identified as a critical contributor for low CEC and LCAT. When stratified into groups based on the presence of cardiometabolic risk factors, we found a prominent reduction in CEC and LCAT as a function of the progressive increase of cardiometabolic risk from 0-2, 0-3 to 0-4/5, whereas an increase in Pre-β-HDL and ApoA-1 glycation was observed between the lowest and highest risk groups. These findings confirm the connection between MS and its predisposing conditions to an impairment of atheroprotective efflux-promoting function of HDLs. Furthermore, we have identified the bona fide pathogenically contribution of abdominal obesity to profound alterations of key metrics of RCT.
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Affiliation(s)
- Jennifer Härdfeldt
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy; INBB, National Institute for Biostructures and Biosystems, Viale delle Medaglie d'Oro 305, 00136 Rome, Italy; Metabolism Unit, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden
| | - Marica Cariello
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Sara Simonelli
- Center E. Grossi Paoletti, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milano, Italy
| | - Alice Ossoli
- Center E. Grossi Paoletti, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milano, Italy
| | - Natasha Scialpi
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Marilidia Piglionica
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy; INBB, National Institute for Biostructures and Biosystems, Viale delle Medaglie d'Oro 305, 00136 Rome, Italy
| | - Emanuela Pasculli
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Alessia Noia
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Elsa Berardi
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Patrizia Suppressa
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Giuseppina Piazzolla
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Carlo Sabbà
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy
| | - Laura Calabresi
- Center E. Grossi Paoletti, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milano, Italy
| | - Antonio Moschetta
- Department of Interdisciplinary Medicine, Aldo Moro University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy; INBB, National Institute for Biostructures and Biosystems, Viale delle Medaglie d'Oro 305, 00136 Rome, Italy; National Cancer Research Center, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
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Changes of Metabolic Biomarker Levels upon One-Year Anti-TNF-α Therapy in Rheumatoid Arthritis and Ankylosing Spondylitis: Associations with Vascular Pathophysiology. Biomolecules 2021; 11:biom11101535. [PMID: 34680168 PMCID: PMC8533731 DOI: 10.3390/biom11101535] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 10/15/2021] [Accepted: 10/15/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. Patients and methods: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. Results: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p < 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p < 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p < 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). Conclusions: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.
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Xu Y, Wang K, Wang Q, Ma Y, Liu X. The Antioxidant Enzyme PON1: A Potential Prognostic Predictor of Acute Ischemic Stroke. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:6677111. [PMID: 33628379 PMCID: PMC7884154 DOI: 10.1155/2021/6677111] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/26/2021] [Accepted: 01/28/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Paraoxonase 1 (PON1) is an antioxidant enzyme, which has been proved to be involved in the pathophysiological process of oxidative stress and various neurological diseases in recent years. Although reduced PON1 activity has been reported in patients with acute ischemic stroke (AIS), the prognostic value of PON1 in AIS has not been clearly established. The purpose of this study was to determine whether the baseline serum PON1 activity level is related to the functional outcome of AIS patients. METHODS From July 2017 to June 2020, AIS patients within 3 days of symptom onset were continuously prospectively included in the study. On admission, clinical and laboratory data were recorded, and serum PON1 activity was tested. The National Institute of Health Stroke Scale (NIHSS) score was used to evaluate the initial neurologic deficit at admission, and the modified Rankin scale (mRS) was used to evaluate the functional outcome at 3 months. A multiple logistic regression model was used to analyze the relationship between the baseline PON1 activity level and the prognosis of AIS. RESULTS A total of 336 AIS patients were finally included in this study. The serum PON1 activity of AIS patients with good outcomes was significantly higher than that of patients with poor outcomes (193.4 ± 16.3 U/mL vs. 127.2 ± 14.9 U/mL, p < 0.001). However, the comparison of other clinical and laboratory data between AIS patients with good and poor outcomes was not significant (p > 0.05). There was a significant decrease in the mRS score in patients with AIS across serum PON1 quartiles (3.0 ± 1.6, 2.6 ± 1.5, 2.4 ± 1.4, and 2.4 ± 1.3, p = 0.007). Multivariate logistic regression analysis showed that the 3-month functional outcome of AIS patients was significantly correlated with the quartile of serum PON1 activity. CONCLUSIONS This study suggests that the serum PON1 activity may be an independent predictor of the functional outcome of AIS patients.
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Affiliation(s)
- Yuzhen Xu
- Department of Neurology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Kai Wang
- Department of Neurology, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Qian Wang
- Department of Central Laboratory, Taian City Central Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong Province, China
| | - Yihong Ma
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Xueyuan Liu
- Department of Neurology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
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13
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Parada-Turska J, Wójcicka G, Beltowski J. Paraoxonase 1 Phenotype and Protein N-Homocysteinylation in Patients with Rheumatoid Arthritis: Implications for Cardiovascular Disease. Antioxidants (Basel) 2020; 9:antiox9090899. [PMID: 32967340 PMCID: PMC7555791 DOI: 10.3390/antiox9090899] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/17/2020] [Accepted: 09/18/2020] [Indexed: 12/13/2022] Open
Abstract
Paraoxonase 1 (PON1) is the high density lipoprotein-associated esterase which inhibits the development of atherosclerosis by metabolizing lipid peroxidation products as well as hydrolyzing proatherogenic metabolite of homocysteine (Hcy), Hcy thiolactone, which otherwise reacts with lysine groups of proteins, thus forming N-Hcy-protein in a process referred to as protein N-homocysteinylation. Rheumatoid arthritis (RA) is the chronic inflammatory autoimmune disease associated with increased risk of cardiovascular complications, but the underlying mechanisms are incompletely understood. We examined PON1 status and N-homocysteinylation of serum proteins in patients with RA. Blood was collected from 74 RA patients and 70 control subjects. PON1 activity was measured toward synthetic (paraoxon, phenyl acetate) and natural (Hcy thiolactone) substrates. PON1 protein concentration was measured by ELISA. Total Hcy as well as N-Hcy-protein were measured in serum as well. PON1 activity toward Hcy thiolactone was lower in RA patients than in control subjects which was accompanied by increased concentration of N-Hcy-protein despite normal total Hcy concentration. PON1 protein concentration was unchanged in the RA group, but the specific enzyme activity was reduced. When RA patients were categorized according to the DAS28-ESR score, PON1 concentration and enzymatic activity were lower whereas N-Hcy-protein was higher in those with high disease activity. PON1 activity and Hcy thiolactone were correlated with DAS28-ESR score and myeloperoxidase concentration. In conclusion, RA is associated with deficiency of PON1 activity and increased protein N-homocyseinylation which may contribute to accelerated development of cardiovascular diseases.
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Affiliation(s)
- Jolanta Parada-Turska
- Department of Rheumatology and Connective Tissue Diseases, Medical University, 20-090 Lublin, Poland;
| | - Grażyna Wójcicka
- Department of Pathophysiology, Medical University, 20-090 Lublin, Poland;
| | - Jerzy Beltowski
- Department of Pathophysiology, Medical University, 20-090 Lublin, Poland;
- Correspondence: ; Tel.: +48-81-4486500
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Fernández-Ortiz AM, Ortiz AM, Pérez S, Toledano E, Abásolo L, González-Gay MA, Castañeda S, González-Álvaro I. Effects of disease activity on lipoprotein levels in patients with early arthritis: can oxidized LDL cholesterol explain the lipid paradox theory? Arthritis Res Ther 2020; 22:213. [PMID: 32917272 PMCID: PMC7488761 DOI: 10.1186/s13075-020-02307-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 08/31/2020] [Indexed: 02/07/2023] Open
Abstract
Background An increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease. Methods We assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44–67] years and disease duration at study entry 5 [3–8] months; and 72% fulfilled the 1987 RA criteria at 2 years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5 years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C. Results After adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios. Conclusions High-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients.
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Affiliation(s)
| | - Ana M Ortiz
- Rheumatology Division, Hospital Universitario La Princesa, IIS-IP, Diego de León 62, 28006, Madrid, Spain
| | - Silvia Pérez
- Rheumatology Division, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - Esther Toledano
- Rheumatology Division, Hospital Clínico San Carlos, IdISSC, Madrid, Spain
| | - Lydia Abásolo
- Rheumatology Division, Hospital Clínico San Carlos, IdISSC, Madrid, Spain
| | - Miguel A González-Gay
- Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDIVAL, University of Cantabria, Santander, Spain
| | - Santos Castañeda
- Rheumatology Division, Hospital Universitario La Princesa, IIS-IP, Diego de León 62, 28006, Madrid, Spain.,Cátedra UAM-Roche, EPID-Future, Universidad Autónoma Madrid, Madrid, Spain
| | - Isidoro González-Álvaro
- Rheumatology Division, Hospital Universitario La Princesa, IIS-IP, Diego de León 62, 28006, Madrid, Spain.
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15
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Association of Paraoxonase1 enzyme and its genetic single nucleotide polymorphisms with cardio-metabolic and neurodegenerative diseases. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100775] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Bassu S, Zinellu A, Sotgia S, Mangoni AA, Floris A, Farina G, Passiu G, Carru C, Erre GL. Oxidative Stress Biomarkers and Peripheral Endothelial Dysfunction in Rheumatoid Arthritis: A Monocentric Cross-Sectional Case-Control Study. Molecules 2020; 25:molecules25173855. [PMID: 32854225 PMCID: PMC7504109 DOI: 10.3390/molecules25173855] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 08/21/2020] [Accepted: 08/24/2020] [Indexed: 02/07/2023] Open
Abstract
Previous studies have suggested that oxidative stress may heighten atherosclerotic burden in rheumatoid arthritis (RA), but direct evidence is lacking. OBJECTIVE To evaluate the relationship between established plasma oxidative stress biomarkers and peripheral endothelial dysfunction (ED), a marker of early atherosclerosis, in RA. METHODS Paroxonase-1 (PON-1), protein-SH (PSH), and malondialdehyde (MDA) were measured in 164 RA patient s and 100 age- and sex-matched healthy controls without previous cardiovascular events. Peripheral ED, evaluated by flow-mediated pulse amplitude tonometry, was defined by log-transformed reactive hyperemia index (Ln-RHI) values < 0.51. RESULTS PON-1 activity and PSH concentrations were significantly reduced in RA patients compared to controls. In regression analysis, increased plasma MDA levels were significantly associated with reduced Ln-RHI [B coefficient (95% CI) = -0.003 (-0.005 to -0.0008), p = 0.008] and the presence of peripheral ED (OR (95% CI) = 1.75 (1.06-2.88), p = 0.028). Contrary to our expectations, increased PON-1 activity was significantly associated, albeit weakly, with the presence of ED (OR (95% CI) = 1.00 (1.00-1.01), p = 0.017). CONCLUSIONS In this first evidence of a link between oxidative stress and markers of atherosclerosis, MDA and PON-1 showed opposite associations with peripheral vasodilatory capacity and the presence of ED in RA. Further studies are needed to determine whether this association predicts atherosclerotic events in the RA population.
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Affiliation(s)
- Stefania Bassu
- Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy; (S.B.); (A.Z.); (S.S.); (G.F.); (C.C.)
| | - Angelo Zinellu
- Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy; (S.B.); (A.Z.); (S.S.); (G.F.); (C.C.)
| | - Salvatore Sotgia
- Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy; (S.B.); (A.Z.); (S.S.); (G.F.); (C.C.)
| | - Arduino Aleksander Mangoni
- Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide 5001, Australia;
- Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01069 Dresden, Germany
| | - Alberto Floris
- Rheumatology Unit, University Clinic and AOU of Cagliari, 09100 Cagliari, Italy;
| | - Giuseppina Farina
- Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy; (S.B.); (A.Z.); (S.S.); (G.F.); (C.C.)
| | - Giuseppe Passiu
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, Università degli Studi di Sassari, 07100 Sassari, Italy;
- Dipartmento di Specialità Mediche, UOC di Reumatologia, Azienda Ospedaliero-Universitaria di Sassari, 07100 Sassari, Italy
| | - Ciriaco Carru
- Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy; (S.B.); (A.Z.); (S.S.); (G.F.); (C.C.)
- Dipartimento di Scienze Biomediche, Azienda Ospedaliero-Universitaria di Sassari, 07100 Sassari, Italy
| | - Gian Luca Erre
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, Università degli Studi di Sassari, 07100 Sassari, Italy;
- Dipartmento di Specialità Mediche, UOC di Reumatologia, Azienda Ospedaliero-Universitaria di Sassari, 07100 Sassari, Italy
- Correspondence: ; Tel.: +39-0792-283-17; Fax: +39-079-216-282
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Ponce-Ruiz N, Murillo-González FE, Rojas-García AE, Barrón-Vivanco BS, Bernal-Hernández YY, González-Arias CA, Ortega-Cervantes L, Ponce-Gallegos J, López-Guarnido O, Medina-Díaz IM. PON1 status and homocysteine levels as potential biomarkers for cardiovascular disease. Exp Gerontol 2020; 140:111062. [PMID: 32827712 DOI: 10.1016/j.exger.2020.111062] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 07/24/2020] [Accepted: 08/16/2020] [Indexed: 11/17/2022]
Abstract
BACKGROUND Cardiovascular disease (CVD) is the leading cause of death. The mainly risks factors for CVD are diabetes, hypertension and high levels of homocysteine (Hcys), among others. Paraoxonase 1 (PON1) has been proposed as an antiatherogenic target for its ability to hydrolyzing oxi-Low-Density-Lipoproteins (LDL) and Hcys-thiolactone. Thus, the aim of the present study was to evaluate the association of Hcys levels, and the activities and concentration of PON1, as well as vitamin B from the diet with a risk for CVD. METHODS A case-control study was carry out in patients with cardiovascular diseases (CVD), Arterial hypertension, but not CVD (AH), and in healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, intake of vitamin B, Hcys, serum amyloid A (SAA), PON1 concentration, and PON1 activities (Arylesterase activity (ARE), Lactonase activity (LAC), and CMPA activity (CMPA)) were evaluated. RESULTS The CVD group had the highest concentration of Hcys and SAA than in the AH and control groups (p < 0.01). ARE, LAC, and CMPA activities and PON1 concentration were lowest in the CVD group. A positive-independent association between Hcys levels and CVD was found (OR = 2.09; 95% CI: 1.69-2.56) and this increase when it was adjusted by age, BMI, ApoA1, vitamin B intake, SAA, and PON1 (OR = 14.41; 95% CI: 1.75-118.71). LAC and CMPA, as well as PON1 concentration, were inversely associated with CVD. CONCLUSION LAC activity, PON1 concentration, and Hcys levels might be good biomarkers for CVD and their association could be modified by the intake of vitamin B.
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Affiliation(s)
- N Ponce-Ruiz
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología, Secretaría de Investigación y Posgrado, Nayarit, Mexico; Posgrado en Ciencias Biológico Agropecuarias, Universidad Autónoma de Nayarit, Tepic, Nayarit, Mexico
| | - F E Murillo-González
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología, Secretaría de Investigación y Posgrado, Nayarit, Mexico; Posgrado en Ciencias Biológico Agropecuarias, Universidad Autónoma de Nayarit, Tepic, Nayarit, Mexico
| | - A E Rojas-García
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología, Secretaría de Investigación y Posgrado, Nayarit, Mexico
| | - B S Barrón-Vivanco
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología, Secretaría de Investigación y Posgrado, Nayarit, Mexico
| | - Y Y Bernal-Hernández
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología, Secretaría de Investigación y Posgrado, Nayarit, Mexico
| | - C A González-Arias
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología, Secretaría de Investigación y Posgrado, Nayarit, Mexico.
| | - L Ortega-Cervantes
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología, Secretaría de Investigación y Posgrado, Nayarit, Mexico
| | | | - O López-Guarnido
- Dept. Legal Medicine and Toxicology, University of Granada School of Medicine, Spain.
| | - I M Medina-Díaz
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología, Secretaría de Investigación y Posgrado, Nayarit, Mexico.
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Screening and Functional Pathway Analysis of Pulmonary Genes Associated with Suppression of Allergic Airway Inflammation by Adipose Stem Cell-Derived Extracellular Vesicles. Stem Cells Int 2020; 2020:5684250. [PMID: 32676117 PMCID: PMC7336241 DOI: 10.1155/2020/5684250] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 05/19/2020] [Accepted: 06/02/2020] [Indexed: 12/26/2022] Open
Abstract
Background Although mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have explored the molecular mechanisms of MSC-derived EVs in allergic airway diseases. The objective of this study was to evaluate differentially expressed genes (DEGs) in the lung associated with the suppression of allergic airway inflammation using adipose stem cell- (ASC-) derived EVs. Methods C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of ASC-derived EVs on allergic airway inflammation, 10 μg/50 μL of EVs were administered intranasally prior to OVA challenge. Lung tissues were removed and DEGs were compared pairwise among the three groups. DEG profiles and hierarchical clustering of the identified genes were analyzed to evaluate changes in gene expression. Real-time PCR was performed to determine the expression levels of genes upregulated after treatment with ASC-derived EVs. Enrichment analysis based on the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed to further identify the function of DEGs. Results Expression of paraoxonase 1 (PON1), brain-expressed X-linked 2 (Bex2), insulin-like growth factor binding protein 6 (Igfbp6), formyl peptide receptor 1 (Fpr1), and secretoglobin family 1C member 1 (Scgb1c1) was significantly increased in asthmatic mice following treatment with ASC-derived EVs. GO enrichment and KEGG pathway analysis showed that these genes were strongly associated with immune system processes and their regulation, cellular processes, single-organism processes, and biological regulation. Conclusion These results suggest that the DEGs identified in this study (PON1, Bex2, Igfbp6, Fpr1, and Scgb1c1) may be involved in the amelioration of allergic airway inflammation by ASC-derived EVs.
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PON-1 haplotype (-108C>T, L55M, and Q192R) modulates the serum levels and activity PONase promoting an atherogenic lipid profile in rheumatoid arthritis patients. Clin Rheumatol 2020; 40:741-752. [PMID: 32556934 DOI: 10.1007/s10067-020-05218-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 04/20/2020] [Accepted: 06/02/2020] [Indexed: 01/10/2023]
Abstract
INTRODUCTION/OBJECTIVE Paraoxonase 1 (PON1) promotes antioxidant and antiatherogenic activity related to the hydrolysis of oxidized lipids of low-density lipoproteins. In rheumatoid arthritis (RA) patients, it has been reported that low PON1 activity is related to an impaired lipid profile, increasing cardiovascular risk (CVR). The goal of this study was to analyze the effect of common PON1 polymorphisms and haplotypes on enzymatic activity, PON1 serum levels (PON1s), and lipid parameters related to atherogenic profile in RA patients. METHODS A cross-sectional study was carried out on 250 Mexican patients with RA. The lipid profile was determined by colorimetric tests. The PON1 activity (CMPAase) was measured by spectrophotometry. The levels of PON1s were determined by ELISA, and the polymorphisms in the PON-1 gene (-108C>T, L55M, and Q192R) were genotyped by the PCR-RFLP method. The haplotypes were estimated and statistical analysis was performed. RESULTS The median of the CMPAase activity and PON1 levels was 13.91 U/mL and 24.75 ng/mL, respectively. The CMPAase activity was significantly lower in carriers of -108TT and 192QQ genotypes (β = - 4.09, P = 0.001 and β = - 3.73, P = 0.002, respectively); moreover, the PON1 levels were lower in 192Q allele carriers (P < 0.01). The TLQ haplotype was associated with CMPAase activity < 13.91 U/mL (OR = 2.29, P < 0.001), as well as with levels of PON1s < 24.75 ng/mL (OR = 1.65, P = 0.017). In this study, the CMPAase activity (< 13.91 U/mL) showed a positive association with lower levels of high-density lipoprotein cholesterol (HDL-c; < 40/50 mg/dL), and with a triglycerides/HDL-c ratio > 3%, and a total cholesterol/HDL-c ratio > 4.5/5%, all representatives of an atherogenic risk lipid profile. CONCLUSIONS PON1 polymorphisms modulate the CMPAase activity and PON1 levels in Mexican patients with RA. The CMPAase activity < 13.91 U/mL is associated with an atherogenic lipid profile, independently of inflammation markers and treatment with anti-rheumatic drugs. Key Points •The haplotype TLQ is a marker for low PONase activity in rheumatoid arthritis. •The haplotype TLQ is a marker for low PON1 serum levels in rheumatoid arthritis. •The enzymatic PON1 activity represents the best marker for an atherogenic lipid profile in rheumatoid arthritis, in comparison with PON1 levels. •The haplotype TLQ is a marker of low PON1 activity, levels of PON1s, and atherogenic lipid profile, independent of treatment therapy in rheumatoid arthritis.
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Atwa ET, Hussin AG, Mohamed MR, Pasha HF, Hammad M. Carotid plaques in adult rheumatoid arthritis patients; association with paroxonase 1 enzymatic activity and Q192R paroxonase 1 gene polymorphism. Mol Biol Rep 2020; 47:4255-4262. [PMID: 32472296 DOI: 10.1007/s11033-020-05558-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 05/23/2020] [Indexed: 01/16/2023]
Abstract
Paroxonase 1 (PON 1) enzymatic activity and Q192R PON polymorphism has been implicated with greater cardiovascular risk in general population. Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized with increased inflammatory markers leading to increased cardiovascular morbidity. The aim of the work was to study association between PON1 enzymatic activity & gene polymorphism with carotid plaques in RA patients. This case-control study was carried out at Zagazig University Hospitals on 99 subjects divided randomly into two groups; 48 RA patients and 51 controls. RA patients fulfilled the revised 2010 EULAR/ACR classification criteria of RA. All patients were subjected to history taking, clinical evaluation, laboratory investigations & plain X-rays. Carotid intima-media thickness (CIMT) and PON1 enzyme assay & genotyping were done for both groups. PON1 enzyme levels were significantly higher in patients than controls. Also, there was a significant negative correlation of PON1 enzyme activity with increased CIMT & plaques. The cut-off value of PON1 enzyme level that had the highest CVD prediction was 4.2 U/ml. Although PON1 genotyping was insignificantly different between patients and controls, patients with QQ genotype had the lowest PON1 activity then patients with QR genotype then RR genotype. In RA patients, decreased serum PON1 enzymatic activity and QQ genotyping of Q192R PON polymorphism was associated with increased CIMT & plaques. Serum PON1 could be a good marker for atherosclerosis prediction in RA patients at cutoff 4.2 U/ml.
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Affiliation(s)
| | | | | | | | - Marwa Hammad
- Faculty of Medicine, Zagazig University, Zagazig, Egypt.
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Dogan İ, Erten S, Sahin A, Isıkoglu S, Neselioglu S, Ergin M, Erel O. Comparison of Oxidant and Antioxidant Parameters in Patients with Sjögren’s Syndrome and Healthy Subjects. AKTUEL RHEUMATOL 2020. [DOI: 10.1055/a-1154-8623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Abstract
Objective Oxidative stress may have an effect on the pathogenesis of diseases, including autoimmune rheumatic diseases. We aimed to investigate the serum paraoxonase activity and other oxidant/antioxidant parameters in patients with Sjögren’s syndrome (SS) and healthy controls.
Methods 85 patients with SS and 65 healthy subjects were included in the study. Groups were age and gender-matched and had no liver disease. Serum paraoxonase (PON)-1 activity, stimulated paraoxonase (SPON), PON-1 phenotypes that represent polymorphism (Q192R; QQ, QR, RR), arylesterase (ARE), total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), advanced oxidative protein products (AOPP), total thioles (TTL) and ischaemia-modified albumin (IMA) were measured in all study participants.
Results Statistically significant differences were found in the QQ and QR+RR phenotype of PON-1 for TAC, TOS and TTL (p<0.001) between SS and healthy groups. The other parameters were statistically insignificant.
Conclusion Antioxidant parameters were lower in SS patients compared with healthy controls. Conversely, oxidant parameters were higher. This imbalance may play a role in SS pathogenesis.
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Affiliation(s)
- İsmail Dogan
- Rheumatology, Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey
| | - Sukran Erten
- Rheumatology, Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey
| | - Ali Sahin
- Rheumatology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Semra Isıkoglu
- Biochemistry, Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey
| | - Salim Neselioglu
- Biochemistry, Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey
| | - Merve Ergin
- Biochemistry, Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey
| | - Ozcan Erel
- Biochemistry, Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey
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Giles JT, Wasko MCM, Chung CP, Szklo M, Blumenthal RS, Kao A, Bokhari S, Zartoshti A, Stein CM, Bathon JM. Exploring the Lipid Paradox Theory in Rheumatoid Arthritis: Associations of Low Circulating Low-Density Lipoprotein Concentration With Subclinical Coronary Atherosclerosis. Arthritis Rheumatol 2019; 71:1426-1436. [PMID: 30883031 DOI: 10.1002/art.40889] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Accepted: 03/12/2019] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Rheumatoid arthritis (RA) patients with the lowest circulating low-density lipoprotein (LDL) concentrations are at heightened risk of cardiovascular events. However, the atherosclerosis burden within this subgroup is unknown. METHODS RA patients pooled from 4 cohort studies of cardiovascular disease (CVD; n = 546) were compared with non-RA controls from the Multi-Ethnic Study of Atherosclerosis (n = 5,279). Those taking lipid-lowering medications were excluded. Differences in cardiac computed tomography-derived Agatston coronary artery calcium (CAC) scores between the RA and control groups were compared across strata of LDL concentration. RESULTS Among those with low LDL concentrations (<70 mg/dl), mean adjusted CAC scores were >4-fold higher for RA patients than for controls (18.6 versus 4.6 Agatston units, respectively; P < 0.001), a difference significantly greater than that in any other LDL concentration stratum except LDL concentration ≥160 mg/dl. Similarly, 32% of the RA patients with low LDL concentration had a CAC score of ≥100 Agatston units compared with only 7% of controls in the same LDL concentration stratum (odds ratio 5.97; P < 0.001), a difference significantly greater than that in all of the other LDL concentration strata. Low LDL concentration was most strongly associated with higher CAC score among RA patients who were white, had ever smoked, or were not obese. Other than a higher frequency of current smokers, RA patients with low LDL concentrations did not have more CVD risk factors or higher measures of RA disease activity or severity than RA patients with higher LDL concentrations. CONCLUSION RA patients with low LDL concentration may represent a group for whom heightened screening and prevention of atherosclerotic CVD is appropriate.
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Affiliation(s)
| | - Mary Chester M Wasko
- Allegheny Health Network, Temple University School of Medicine, Pittsburgh, Pennsylvania
| | | | | | | | - Amy Kao
- EMD Serono Research & Development Institute, Inc., Billerica, Maryland
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Reiss AB, Silverman A, Khalfan M, Vernice NA, Kasselman LJ, Carsons SE, De Leon J. Accelerated Atherosclerosis in Rheumatoid Arthritis: Mechanisms and Treatment. Curr Pharm Des 2019; 25:969-986. [DOI: 10.2174/1381612825666190430113212] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 04/14/2019] [Indexed: 12/11/2022]
Abstract
Background:Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disorder that increases the risk of developing cardiovascular disease. There is accumulating evidence that the RA disease state accelerates the formation of atherosclerotic plaques. Treatments for RA improve joint symptomatology and may reduce inflammation, but consideration of their effects on the cardiovascular system is generally low priority.Objective:Since cardiovascular disease is the leading cause of mortality in RA patients, the impact of RA therapies on atherosclerosis is an area in need of attention and the focus of this review.Results:The drugs used to treat RA may be analgesics, conventional disease-modifying anti-rheumatic drugs, and/or biologics, including antibodies against the cytokine tumor necrosis factor-α. Pain relievers such as nonselective non-steroidal anti-inflammatory drugs and cyclooxygenase inhibitors may adversely affect lipid metabolism and cyclooxygenase inhibitors have been associated with increased adverse cardiovascular events, such as myocardial infarction and stroke. Methotrexate, the anchor disease-modifying anti-rheumatic drug in RA treatment has multiple atheroprotective advantages and is often combined with other therapies. Biologic inhibitors of tumor necrosis factor-α may be beneficial in preventing cardiovascular disease because tumor necrosis factor-α promotes the initiation and progression of atherosclerosis. However, some studies show a worsening of the lipid profile in RA with blockade of this cytokine, leading to higher total cholesterol and triglycerides.Conclusion:Greater understanding of the pharmacologic activity of RA treatments on the atherosclerotic process may lead to improved care, addressing both damages to the joints and heart.
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Affiliation(s)
- Allison B. Reiss
- Winthrop Research Institute, Department of Medicine, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, United States
| | - Andrew Silverman
- Winthrop Research Institute, Department of Medicine, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, United States
| | - Muhammed Khalfan
- Winthrop Research Institute, Department of Medicine, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, United States
| | - Nicholas A. Vernice
- Winthrop Research Institute, Department of Medicine, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, United States
| | - Lora J. Kasselman
- Winthrop Research Institute, Department of Medicine, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, United States
| | - Steven E. Carsons
- Winthrop Research Institute, Department of Medicine, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, United States
| | - Joshua De Leon
- Winthrop Research Institute, Department of Medicine, NYU Winthrop Hospital, 101 Mineola Boulevard, Suite 4-004, Mineola, NY 11501, United States
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Bae SC, Lee YH. Associations between paraoxonase 1 (PON1) polymorphisms and susceptibility and PON1 activity in rheumatoid arthritis patients, and comparison of PON1 activity in patients and controls: a meta-analysis. Clin Rheumatol 2019; 38:2141-2149. [DOI: 10.1007/s10067-019-04499-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 02/08/2019] [Accepted: 03/04/2019] [Indexed: 02/03/2023]
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Fernández-Torres J, Martínez-Nava GA, Zamudio-Cuevas Y, Martínez-Flores K, Espinosa-Morales R. Epistasis between ADIPOQ rs1501299 and PON1 rs662 polymorphisms is potentially associated with the development of knee osteoarthritis. Mol Biol Rep 2019; 46:2049-2058. [PMID: 30734899 DOI: 10.1007/s11033-019-04654-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 01/24/2019] [Indexed: 01/08/2023]
Abstract
Overweight produces oxidative stress (OS) on the articular cartilage, with the subsequent risk of developing knee osteoarthritis (OA). Associations between genetic polymorphisms related to OS and OA have been reported, but it is currently unknown whether there exist interactions among them that affect OA development. To identify and evaluate interactions between multiple SNPs related to OS in Mexican knee OA patients. Ninety-two knee OA patients were included in the study, which were compared to 147 healthy controls. Nine variants of six genes (PEPD, AGER, IL6, ADIPOQ, PON1, and CA6) related to OS were genotyped in both study groups through the OpenArray system. Epistasis was analyzed with the multifactor dimensionality reduction (MDR) method. The MDR analysis revealed a significant interaction (p = 0.0107) between polymorphisms rs1501299 (ADIPOQ) and rs662 (PON1), with an entropy value of 9.84%; in addition, high and low risk genotypes were identified between these two polymorphisms. The effect of the interaction between rs1501299 (ADIPOQ) and rs662 (PON1) polymorphisms seems to play an important role in OA pathogenesis; so the epistasis analysis may provide an excellent tool for identifying individuals at high risk for developing OA.
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Affiliation(s)
- Javier Fernández-Torres
- Synovial Fluid Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico City, Mexico.
| | - Gabriela Angélica Martínez-Nava
- Synovial Fluid Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico City, Mexico
| | - Yessica Zamudio-Cuevas
- Synovial Fluid Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico City, Mexico
| | - Karina Martínez-Flores
- Synovial Fluid Laboratory, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico City, Mexico
| | - Rolando Espinosa-Morales
- Rheumatology Department, Instituto Nacional de Rehabilitación "Luis Guillermo Ibarra Ibarra", Calzada Mexico-Xochimilco 289, Col. Arenal de Guadalupe, Tlalpan, 14389, Mexico City, Mexico
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Ghaedi E, Moradi S, Aslani Z, Kord-Varkaneh H, Miraghajani M, Mohammadi H. Effects of grape products on blood lipids: a systematic review and dose–response meta-analysis of randomized controlled trials. Food Funct 2019; 10:6399-6416. [DOI: 10.1039/c9fo01248f] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Grape products through several plausible mechanisms-of-action are reported to improve lipid profile. The present systematic review revealed that grape product supplementation might have a positive effect on achieving a lipid profile target.
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Affiliation(s)
- Ehsan Ghaedi
- Students’ Scientific Research Center (SSRC)
- Tehran University of Medical Sciences (TUMS)
- Tehran
- Iran
- Department of Cellular and Molecular Nutrition
| | - Sajjad Moradi
- Halal Research Centre of IRI
- FDA
- Tehran
- Iran
- Nutritional Sciences Department
| | - Zahra Aslani
- Department of Community Nutrition
- School of Nutritional Sciences and Dietetics
- Tehran University of Medical Sciences
- Tehran
- Iran
| | - Hamed Kord-Varkaneh
- Student Research Committee
- Department of Clinical Nutrition and Dietetics
- Faculty of Nutrition and Food Technology
- Shahid Beheshti University of Medical Sciences
- Tehran
| | - Maryam Miraghajani
- National Nutrition and Food Technology Research Institute
- Shahid Beheshti University of Medical Sciences
- Tehran
- Iran
- The Early Life Research Unit
| | - Hamed Mohammadi
- Student Research Committee
- Department of Clinical Nutrition
- School of Nutrition and Food Science
- Isfahan University of Medical Sciences
- Isfahan
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27
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Correlation of Paraoxonase-1 with the Severity of Crohn's Disease. Molecules 2018; 23:molecules23102603. [PMID: 30314292 PMCID: PMC6222603 DOI: 10.3390/molecules23102603] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 10/05/2018] [Accepted: 10/08/2018] [Indexed: 12/17/2022] Open
Abstract
Diagnostics of Crohn’s disease (CD) requires noninvasive biomarkers facilitating early detection and differentiation of the disease. Therefore, in this study, we aimed to determine the relationship between paraoxonase-1 (PON-1), the severity of CD, oxidative stress, and inflammation in CD. The CD activity index was based on the current classification. Plasma PON-1 was measured in 47 patients with CD, and in 23 control volunteers. Using quantitative variables such as receiver operating characteristics (ROC) (area under the curve (AUC)), the diagnostic utility of PON-1 in differentiating the severity of CD was assessed. Circulating PON-1 was found to be decreased in the CD group compared to the control group (269.89 vs. 402.56 U/L, respectively), and it correlated well with the disease activity. PON-1 correlated positively with hemoglobin (Hb) (r = 0.539, p < 0.001), hematocrit (Ht) (r = 0.48, p < 0.001), total cholesterol (TC) (r = 0.343, p < 0.001), high density lipoprotein (HDL) (r = 0.536, p < 0.001), low density lipoprotein (LDL) (r = 0.54, p < 0.001), and triglyceride (TG) (r = 0.561, p < 0.001) and correlated negatively with white blood cell count (WBC) (r = −0.262, p = 0.029), platelet count (PLT) (r = −0.326, p = 0.006), C-reactive protein (CRP) (r = −0.61, p < 0.001), and malondialdehyde (MDA) (r = −0.924, p < 0.001). PON-1 as a marker for CD differentiation possessed a sensitivity and specificity of 93.62% and 91.30%, respectively. CD was found to be associated with the decrease in the levels of PON-1, which correlates well with activity of the disease and reflects the intensification of inflammation, as well as intensified lipid peroxidation. High sensitivity and specificity of PON-1 determines its selection as a good screening test for CD severity.
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Pedret A, Fernández-Castillejo S, Valls RM, Catalán Ú, Rubió L, Romeu M, Macià A, López de Las Hazas MC, Farràs M, Giralt M, Mosele JI, Martín-Peláez S, Remaley AT, Covas MI, Fitó M, Motilva MJ, Solà R. Cardiovascular Benefits of Phenol-Enriched Virgin Olive Oils: New Insights from the Virgin Olive Oil and HDL Functionality (VOHF) Study. Mol Nutr Food Res 2018; 62:e1800456. [PMID: 29956886 PMCID: PMC8456742 DOI: 10.1002/mnfr.201800456] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Indexed: 01/09/2023]
Abstract
SCOPE The main findings of the "Virgin Olive Oil and HDL Functionality" (VOHF) study and other related studies on the effect of phenol-enriched virgin olive oil (VOO) supplementation on cardiovascular disease are integrated in the present work. METHODS AND RESULTS VOHF assessed whether VOOs, enriched with their own phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and functionality of HDL. In this randomized, double-blind, crossover, and controlled trial, 33 hypercholesterolemic subjects received a control VOO (80 mg kg-1 ), FVOO (500 mg kg-1 ), and FVOOT (500 mg kg-1 ; 1:1) for 3 weeks. Both functional VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat-soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing fecal microbial metabolic activity. Additional cardioprotective benefits were observed according to phenol source and content in the phenol-enriched VOOs. These insights support the beneficial effects of OO and PC from different sources. CONCLUSION Novel therapeutic strategies should increase HDL-cholesterol levels and enhance HDL functionality. The tailoring of phenol-enriched VOOs is an interesting and useful strategy for enhancing the functional quality of HDL, and thus, it can be used as a complementary tool for the management of hypercholesterolemic individuals.
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Affiliation(s)
- Anna Pedret
- Eurecat, Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, Functional Nutrition, Oxidation, and CVD Research Group (NFOC-Salut), 43204, Reus, Spain
- Facultat de Medicina i Ciències de la Salut, Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Universitat Rovira i Virgili, 43201, Reus, Spain
| | - Sara Fernández-Castillejo
- Facultat de Medicina i Ciències de la Salut, Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Universitat Rovira i Virgili, 43201, Reus, Spain
- Institut d'Investigació Sanitaria Pere Virgili, 43204, Reus, Spain
| | - Rosa-Maria Valls
- Facultat de Medicina i Ciències de la Salut, Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Universitat Rovira i Virgili, 43201, Reus, Spain
| | - Úrsula Catalán
- Facultat de Medicina i Ciències de la Salut, Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Universitat Rovira i Virgili, 43201, Reus, Spain
- Institut d'Investigació Sanitaria Pere Virgili, 43204, Reus, Spain
| | - Laura Rubió
- Facultat de Medicina i Ciències de la Salut, Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Universitat Rovira i Virgili, 43201, Reus, Spain
- Antioxidants Research Group, Food Technology Department, Universitat de Lleida-Agrotecnio Center, 25198, Lleida, Spain
| | - Marta Romeu
- Facultat de Medicina i Ciències de la Salut, Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Universitat Rovira i Virgili, 43201, Reus, Spain
| | - Alba Macià
- Antioxidants Research Group, Food Technology Department, Universitat de Lleida-Agrotecnio Center, 25198, Lleida, Spain
| | - Maria Carmen López de Las Hazas
- Antioxidants Research Group, Food Technology Department, Universitat de Lleida-Agrotecnio Center, 25198, Lleida, Spain
- Laboratory of Epigenetics of Lipid Metabolism, Instituto Madrileño de Estudios Avanzados-Alimentación, CEI UAM+CSIC, 28049, Madrid, Spain
| | - Marta Farràs
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, 08025, Barcelona, Spain
- Cardiovascular Risk and Nutrition Research Group, REGICOR Study Group, Hospital del Mar Research Institute (IMIM), 08003, Barcelona, Spain
| | - Montse Giralt
- Facultat de Medicina i Ciències de la Salut, Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Universitat Rovira i Virgili, 43201, Reus, Spain
| | - Juana I Mosele
- Antioxidants Research Group, Food Technology Department, Universitat de Lleida-Agrotecnio Center, 25198, Lleida, Spain
- Instituto de Bioquímica y Medicina Molecular (IBIMOL), CONICET - Universidad de Buenos Aires, 1053, Buenos Aires, Argentina
- Facultad de Farmacia y Bioquímica, Departamento de Química Analítica y Fisicoquímica, Cátedra de Fisicoquímica, Universidad de Buenos Aires, C1113AAD, Buenos Aires, Argentina
| | - Sandra Martín-Peláez
- Spanish Biomedical Research Networking Centre (CIBER), Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029, Madrid, Spain
- Cardiovascular Risk and Nutrition Research Group, REGICOR Study Group, Hospital del Mar Research Institute (IMIM), 08003, Barcelona, Spain
| | - Alan T Remaley
- Department of Laboratory Medicine Clinical Center, National Institutes of Health, 20814, Bethesda, MD, USA
- Lipoprotein Metabolism Section Cardio-Pulmonary Branch National Heart, Lung and Blood Institute National Institutes of Health, 20814, Bethesda, MD, USA
| | - Maria-Isabel Covas
- Spanish Biomedical Research Networking Centre (CIBER), Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029, Madrid, Spain
- Cardiovascular Risk and Nutrition Research Group, REGICOR Study Group, Hospital del Mar Research Institute (IMIM), 08003, Barcelona, Spain
- NUPROAS (Nutritional Project Assessment), Handesbolag (NUPROAS HB), 13100, Nacka, Sweden
| | - Montse Fitó
- Spanish Biomedical Research Networking Centre (CIBER), Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029, Madrid, Spain
- Cardiovascular Risk and Nutrition Research Group, REGICOR Study Group, Hospital del Mar Research Institute (IMIM), 08003, Barcelona, Spain
| | - Maria-José Motilva
- Antioxidants Research Group, Food Technology Department, Universitat de Lleida-Agrotecnio Center, 25198, Lleida, Spain
| | - Rosa Solà
- Facultat de Medicina i Ciències de la Salut, Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Universitat Rovira i Virgili, 43201, Reus, Spain
- Institut d'Investigació Sanitaria Pere Virgili, 43204, Reus, Spain
- Hospital Universitari Sant Joan de Reus, 43204, Reus, Spain
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Serum Amyloid A, Paraoxonase-1 Activity, and Apolipoprotein Concentrations as Biomarkers of Subclinical Atherosclerosis Risk in Adrenal Incidentaloma Patients. Arch Med Res 2018; 49:182-190. [PMID: 30031631 DOI: 10.1016/j.arcmed.2018.07.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Accepted: 07/02/2018] [Indexed: 11/21/2022]
Abstract
BACKGROUND Adrenal incidentalomas (AIs), particularly subclinical hypercortisolism (SH), are related to an increased risk of atherosclerosis. The anti-oxidative enzyme paraoxonase-1 (PON1) and the acute phase reactant serum amyloid A (SAA) are transported by highdensity lipoprotein and reciprocally regulated in acute inflammatory response. Our aim was to investigate serum SAA, PON1, and apolipoprotein levels as indicators of subclinical atherosclerosis in patients with nonfunctioning AI (NFAI) and SH. METHODS The study group consisted of 60 controls, 14 SH, and 86 NFAI subjects. Serum amyloid A (SAA), PON1 activity, lipid profiles, apoA and B, lipoprotein A (LpA), hsCRP, and HOMA-IR levels were compared in all groups. RESULTS Serum insulin, triglyceride, SAA, SAA/PON1 ratio, LpA, apoB, hsCRP, and morning cortisol levels were found to be higher while PON1 and apoAI levels were lower in the SH and NFAI groups compared with the controls, and these parameters were found to be more impaired in SH group than NFAI group (p <0.001). HOMA-IR was higher and DHEAS was lower in the SH group than in the other groups. The SAA/PON1 ratio was positively correlated with LpA (r = 0.460; p <0.001), apoB (r = 0.515; p <0.001), insulin (r = 0.275; p = 0.026), triglyceride (r = 0.248; p = 0.002), morning cortisol (r = 0.259; p = 0.045), and UFC (r = 0.274; p <0.001) and negatively correlated with apoAI (r = 0.329; p <0.001), ACTH (r = -0.384; p <0.001), and DHEAS (r = -0.521, p <0.001) levels. The cut-off value of the SAA/PON1 ratio for NFAI was >0.23, and for SH it was >1.33. CONCLUSION The serum SAA/PON1 ratio was high in both the NFAI and SH groups and also exhibited higher levels in SH group. An increased SAA/PON1 ratio and low DHEAS could be attributable to subclinical atherosclerosis risk in SH patients.
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Husni ME, Wilson Tang WH, Lucke M, Chandrasekharan UM, Brennan DM, Hazen SL. Correlation of High-Density Lipoprotein-Associated Paraoxonase 1 Activity With Systemic Inflammation, Disease Activity, and Cardiovascular Risk Factors in Psoriatic Disease. Arthritis Rheumatol 2018; 70:1240-1250. [PMID: 29569857 DOI: 10.1002/art.40499] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 03/13/2018] [Indexed: 11/10/2022]
Abstract
OBJECTIVE To compare the activity of high-density lipoprotein (HDL)-associated paraoxonase 1 (PON1) in patients with psoriasis (PsO) and patients with psoriatic arthritis (PsA), and to evaluate the association of PON1 activity with the extent of disease activity and severity of the cardiovascular disease (CVD) burden in these patients. METHODS Serum levels of paraoxonase and arylesterase activity (both measures of PON1 function in humans) were measured in patients with PsA (n = 198, 51.0% male) and patients with PsO (n = 145, 50.3% male) who were enrolled in a longitudinal psoriatic disease biorepository. Data on PsA disease activity (using the Disease Activity Score in 28 joints [DAS28], Clinical Disease Activity Index, and painful/swollen joint counts), preexistent CVD and CVD risk factors (including diabetes, dyslipidemia, hypertension, and smoking), Framingham Risk Scores for CVD, quality of life measures, and laboratory test findings (erythrocyte sedimentation rate, C-reactive protein level, and lipid profiles) were recorded. RESULTS Serum arylesterase activities were significantly lower in patients with PsO and patients with PsA (mean ± SD 111.1 ± 25.5 μmoles/minute/ml and 124.4 ± 33.4 μmoles/minute/ml, respectively) compared to healthy controls (144.3 ± 33.4 μmoles/minute/ml) (each P < 0.001 versus healthy controls). Serum arylesterase activity decreased in parallel with increasing levels of disease activity (DAS28 scores, P = 0.012), older age (P = 0.013), higher body mass index (P = 0.042), greater incidence of metabolic syndrome (P = 0.004) and hypertension (P = 0.014), and worsening Framingham Risk Scores (P = 0.001). However, no correlation was seen between serum arylesterase activity and the extent of disease activity or CVD burden in patients with PsO. Serum paraoxonase activity trended lower both in patients with PsO and in patients with PsA (each P = 0.073 versus healthy controls). However, no association was seen between serum paraoxonase activity and the extent of disease activity or CVD burden in either of the patient cohorts. CONCLUSION PON1 activity is decreased in psoriatic diseases. In the PsA cohort, decreases in arylesterase activity correlated with increasing severity of joint disease and CVD burden. Arylesterase activity, as compared to paraoxonase activity, appeared to serve as a more sensitive predictor of preexisting CV risk factors in the PsA cohort. However, this correlation was not observed in the PsO population.
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Cardiovascular Safety of Biologics and JAK Inhibitors in Patients with Rheumatoid Arthritis. Curr Rheumatol Rep 2018; 20:42. [DOI: 10.1007/s11926-018-0752-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Xu H, Qu Y. Correlation of PON1 polymorphisms with ankylosing spondylitis susceptibility: A case-control study in Chinese Han population. Medicine (Baltimore) 2017; 96:e7416. [PMID: 29049176 PMCID: PMC5662342 DOI: 10.1097/md.0000000000007416] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Paraoxonase 1 (PON1) modulates the oxidative stress and inflammatory response, thus, it might relate to the risk of ankylosing spondylitis (AS). The aim of present study was to discover the correlation of PON1 polymorphisms (rs662 and rs854560) with PON1 activity and AS risk.Around 128 AS patients and 146 healthy controls were recruited in this case-control study. PON1 polymorphisms were genotyped by direct sequencing. Serum PON1 activity was detected and compared by nonparametric test in different genotypes of PON1 polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to present the relative risk for AS.GG genotype and G allele of rs662 polymorphism were closely correlated with enhanced AS risk (P = .034, OR = 2.318, 95%CI = 1.051-5.113; P = .032, OR = 1.485, 95%CI = 1.033-2.135). PON1 activity was obviously higher in controls than that in AS patients. Significant difference of PON1 activity has been discovered in the different rs662 genotypes (P < .01). rs662 GG genotype carriers had the lowest PON1 activity, followed by AG carriers and the AA carriers. Besides, no significant relationship existed between rs854560 genotypes and AS risk.PON1 rs662 polymorphism is significantly correlated with increased AS risk via inhibiting PON1 activity.
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Chen WQ, Xie ZZ, Wang X, Zhao JH, Hu Q, Chen YH, Gao WY, Liu Y. Influences of PON1 on airway inflammation and remodeling in bronchial asthma. J Cell Biochem 2017; 119:793-805. [PMID: 28657647 DOI: 10.1002/jcb.26242] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Accepted: 06/27/2017] [Indexed: 01/31/2023]
Abstract
This study aims to explore the influences of Paraoxonase-1 (PON1) involved in airway inflammation and remodeling in asthma. Mice were divided into control, asthma, asthma + PON1 and asthma + NC groups, and asthma models were established via aerosol inhalation of ovalbumin (OVA). HE, Masson, and PAS stains were used to observe airway inflammation and remodeling, Giemsa staining to assess inflammatory cells in bronchoalveolar lavage fluid (BALF), qRT-PCR and Western blot to detect PON1 expression, lipid peroxidation and glutathione assays to quantify malondialdehyde (MDA) activity and glutathione peroxidase (GSH) levels, ELISA to determine inflammatory cytokines and immunoglobulin, and colorimetry to detect PON1 activities. Additionally, mice lung macrophages and fibroblasts were transfected with PON1 plasmid in vitro; ELISA and qRT-PCR were performed to understand the effects of PON1 on inflammatory cytokines secreted by lung macrophages, MTT assay for lung fibroblasts proliferation and qRT-PCR and Western blot for the expressions of PON1, COL1A1, and fibronectin. After overexpression of PON1, the asthma mice had decreased inflammatory cell infiltration, fibrosis degree, and airway wall thickness; inflammatory cells and inflammatory cytokines in BALF were also reduced, expressions of OVA-IgE and IgG1, and MDA activity were decreased, but the expressions of OVA-IgG2a and INF-γ and GSH levels were increased. Besides, PON1 significantly inhibited microphage expression of LPS-induced inflammatory cytokines, lung fibroblast proliferation, and COL1A1 and fibronectin expression. Thus, PON1 could relieve airway inflammation and airway remodeling in asthmatic mice and inhibit the secretion of LPS-induced macrophage inflammatory cytokines and the proliferation of lung fibroblasts.
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Affiliation(s)
- Wei-Qiang Chen
- Department of Respiratory and Critical Care Medicine, No.2 People's Hospital of Kunming, Kunming, Yunnan Province, P.R. China
| | - Zuo-Zhou Xie
- Department of Respiratory and Critical Care Medicine, No.2 People's Hospital of Kunming, Kunming, Yunnan Province, P.R. China
| | - Xiang Wang
- Department of Respiratory and Critical Care Medicine, No.2 People's Hospital of Kunming, Kunming, Yunnan Province, P.R. China
| | - Jin-Hong Zhao
- Department of Respiratory and Critical Care Medicine, No.2 People's Hospital of Kunming, Kunming, Yunnan Province, P.R. China
| | - Qin Hu
- Department of Respiratory and Critical Care Medicine, No.2 People's Hospital of Kunming, Kunming, Yunnan Province, P.R. China
| | - Ying-Hua Chen
- Department of Respiratory and Critical Care Medicine, No.2 People's Hospital of Kunming, Kunming, Yunnan Province, P.R. China
| | - Wen-Yong Gao
- Department of Respiratory and Critical Care Medicine, No.2 People's Hospital of Kunming, Kunming, Yunnan Province, P.R. China
| | - Yi Liu
- Department of Respiratory and Critical Care Medicine, No.2 People's Hospital of Kunming, Kunming, Yunnan Province, P.R. China
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Fernández-Castillejo S, García-Heredia AI, Solà R, Camps J, López de la Hazas MC, Farràs M, Pedret A, Catalán Ú, Rubió L, Motilva MJ, Castañer O, Covas MI, Valls RM. Phenol-enriched olive oils modify paraoxonase-related variables: A randomized, crossover, controlled trial. Mol Nutr Food Res 2017; 61. [PMID: 28544610 DOI: 10.1002/mnfr.201600932] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Revised: 04/20/2017] [Accepted: 04/21/2017] [Indexed: 12/18/2022]
Abstract
SCOPE Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic of cardiovascular disease. Our aim was to assess short- and long-term effects of virgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with them plus complementary PC from thyme (FVOOT), on PON-related variables and the mechanisms involved. METHODS AND RESULTS Two randomized, controlled, double-blind, and crossover interventions were conducted. In an acute intake study, participants ingested three FVOOs differing in PC content. In a sustained intake study, participants ingested a control VOO and two different FVOOs with the same PC content but differing in PC source. Acute and sustained intake of VOO and FVOO decreased PON1 protein and increased PON1-associated specific activities, while FVOOT yielded opposite results. PON3 protein levels increased only after sustained consumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolated PC from VOO and from thyme modulate mitogen-activated protein kinases and peroxisome proliferator-activated receptors regulating PON synthesis, while a combination of these PCs cancels such regulation. CONCLUSION This study reveals that the intake of phenol-enriched FVOOs modulates oxidative balance by modifying PON-related variables according to PC content and source, and this modulation can be perceived as beneficial.
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Affiliation(s)
- Sara Fernández-Castillejo
- Research Unit on Lipids and Atherosclerosis, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Functional Nutrition, Oxidation and Cardiovascular Disease (NFOC-SALUT) group, Universitat Rovira i Virgili, Reus, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Ana-Isabel García-Heredia
- Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain
| | - Rosa Solà
- Research Unit on Lipids and Atherosclerosis, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Functional Nutrition, Oxidation and Cardiovascular Disease (NFOC-SALUT) group, Universitat Rovira i Virgili, Reus, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Jordi Camps
- Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain
| | | | - Marta Farràs
- Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.,Cardiovascular Risk and Nutrition Research group, IMIM- Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.,CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Anna Pedret
- Research Unit on Lipids and Atherosclerosis, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Functional Nutrition, Oxidation and Cardiovascular Disease (NFOC-SALUT) group, Universitat Rovira i Virgili, Reus, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Úrsula Catalán
- Research Unit on Lipids and Atherosclerosis, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Functional Nutrition, Oxidation and Cardiovascular Disease (NFOC-SALUT) group, Universitat Rovira i Virgili, Reus, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Laura Rubió
- Research Unit on Lipids and Atherosclerosis, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Functional Nutrition, Oxidation and Cardiovascular Disease (NFOC-SALUT) group, Universitat Rovira i Virgili, Reus, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.,Department of Food Technology, Agrotecnio Center, University of Lleida, Lleida, Spain
| | - Maria-José Motilva
- Department of Food Technology, Agrotecnio Center, University of Lleida, Lleida, Spain
| | - Olga Castañer
- Cardiovascular Risk and Nutrition Research group, IMIM- Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.,CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - María-Isabel Covas
- Cardiovascular Risk and Nutrition Research group, IMIM- Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.,CIBER de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.,NUPROAS (Nutritional Project Assessment), Handesbolag (NUPROAS HB), Nacka, Sweden
| | - Rosa-Maria Valls
- Research Unit on Lipids and Atherosclerosis, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili (IISPV), Functional Nutrition, Oxidation and Cardiovascular Disease (NFOC-SALUT) group, Universitat Rovira i Virgili, Reus, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
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Lauper K, Gabay C. Cardiovascular risk in patients with rheumatoid arthritis. Semin Immunopathol 2017; 39:447-459. [PMID: 28455580 DOI: 10.1007/s00281-017-0632-2] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Accepted: 04/10/2017] [Indexed: 02/06/2023]
Abstract
Substantial epidemiologic data have shown an increased risk of cardiovascular (CV) disease in rheumatoid arthritis (RA) patients. Traditional CV risk factors may partly contribute to CV disease in RA; however, current evidence underlines the important role of inflammation in the pathogenesis of atherosclerosis and amplification of CV risk. Interplays between inflammation and lipid metabolism in the development of atherosclerosis have been established by recent scientific advances. Atherosclerosis is currently viewed as an inflammatory disease, and modifications of lipoproteins during inflammation accelerate atherogenesis. The role of inflammation in the increased CV risk in RA has been further demonstrated by the CV protective effect of methotrexate and TNF antagonists, particularly in patients responding to these treatments. The management of CV risk in RA should include the use of effective disease-modifying anti-rheumatic drugs to control disease activity and the treatment of traditional CV risk factors.
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Affiliation(s)
- Kim Lauper
- Division of Rheumatology, University Hospitals of Geneva, 26 Avenue Beau-Séjour, 1206, Geneva, Switzerland
| | - Cem Gabay
- Division of Rheumatology, University Hospitals of Geneva, 26 Avenue Beau-Séjour, 1206, Geneva, Switzerland.
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Chang TI, Streja E, Moradi H. Could high-density lipoprotein cholesterol predict increased cardiovascular risk? Curr Opin Endocrinol Diabetes Obes 2017; 24:140-147. [PMID: 28099207 DOI: 10.1097/med.0000000000000318] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE OF REVIEW Serum high-density lipoprotein (HDL) is considered to be protective against cardiovascular disease. However, there is emerging evidence that under certain conditions the HDL molecule can become dysfunctional and proinflammatory, paradoxically leading to increased risk of cardiovascular disease. This review will provide a brief outline of the potential mechanisms by which HDL can become atherogenic and summarize some of the clinical evidence on this topic. RECENT FINDINGS HDL metabolism, structure, and function in addition to its level can be profoundly altered under conditions of marked oxidative stress and chronic inflammation. These abnormalities, in turn, lead to impaired reverse cholesterol transport, increased systemic oxidative stress/inflammation, and endothelial dysfunction that subsequently may contribute to atherogenesis and progression of cardiovascular disease. SUMMARY Association of serum HDL cholesterol level with outcomes is not only dependent on its serum concentration but also on the qualities/properties of this lipoprotein at a given point in time. Hence, it is essential that future studies examining association of HDL with risk of cardiovascular disease take into account the complexities of HDL metabolism and function and address the impact of the HDL particle as a whole (quantity as well as various properties) on atherosclerosis and cardiovascular outcomes.
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Affiliation(s)
- Tae Ik Chang
- aHarold Simmons Center for Kidney Disease Research and Epidemiology, School of Medicine, University of California, Irvine, Orange, California, USA bDepartment of Internal Medicine, NHIS Medical Center, Ilsan Hospital, Goyangshi, Gyeonggi-do, Republic of Korea cDepartment of Medicine, Long Beach Veteran Affairs Health System, Long Beach, California, USA
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Medina-Díaz IM, Ponce-Ruiz N, Ramírez-Chávez B, Rojas-García AE, Barrón-Vivanco BS, Elizondo G, Bernal-Hernández YY. Downregulation of human paraoxonase 1 (PON1) by organophosphate pesticides in HepG2 cells. ENVIRONMENTAL TOXICOLOGY 2017; 32:490-500. [PMID: 26948828 DOI: 10.1002/tox.22253] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 02/09/2016] [Accepted: 02/14/2016] [Indexed: 06/05/2023]
Abstract
Paraoxonase 1 (PON1) is a calcium-dependent esterase synthesized primarily in the liver and secreted into the plasma where it is associated with high-density lipoproteins (HDL). PON1 hydrolyzes and detoxifies some toxic metabolites of organophosphorus compounds (OPs) such as methyl parathion and chlorpyrifos. Thus, PON1 activity and expression levels are important for determining susceptibility against OPs poisoning. Some studies have demonstrated that OPs can modulate gene expression through interactions with nuclear receptors. In this study, we evaluated the effects of methyl parathion and chlorpyrifos on the modulation of PON1 in Human Hepatocellular Carcinoma (HepG2) cells by real-time PCR, PON1 activity assay, and western blot. The results showed that the treatments with methyl parathion and chlorpyrifos decreased PON1 mRNA and immunoreactive protein and increased inflammatory cytokines in HepG2 cells. The effects of methyl parathion and chlorpyrifos on the downregulation of PON1 gene expression in HepG2 cells may provide evidence of OPs cytotoxicity related to oxidative stress and an inflammatory response. A decrease in the expression of the PON1 gene may increase the susceptibility to OPs intoxication and the risk of diseases related to inflammation and oxidative stress. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 490-500, 2017.
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Affiliation(s)
- Irma Martha Medina-Díaz
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado
| | - Néstor Ponce-Ruiz
- Posgrado en Ciencias Biológico Agropecuarias, Universidad Autónoma de Nayarit
| | | | - Aurora Elizabeth Rojas-García
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado
| | - Briscia S Barrón-Vivanco
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado
| | - Guillermo Elizondo
- Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, México, D.F., México
| | - Yael Y Bernal-Hernández
- Universidad Autónoma de Nayarit, Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado
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Abstract
PURPOSE OF REVIEW Studies have shown that chronic inflammatory disorders, such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis are associated with an increased risk of atherosclerotic cardiovascular disease. The mechanism by which inflammation increases cardiovascular disease is likely multifactorial but changes in HDL structure and function that occur during inflammation could play a role. RECENT FINDINGS HDL levels decrease with inflammation and there are marked changes in HDL-associated proteins. Serum amyloid A markedly increases whereas apolipoprotein A-I, lecithin:cholesterol acyltransferase, cholesterol ester transfer protein, paraoxonase 1, and apolipoprotein M decrease. The exact mechanism by which inflammation decreases HDL levels is not defined but decreases in apolipoprotein A-I production, increases in serum amyloid A, increases in endothelial lipase and secretory phospholipase A2 activity, and decreases in lecithin:cholesterol acyltransferase activity could all contribute. The changes in HDL induced by inflammation reduce the ability of HDL to participate in reverse cholesterol transport and protect LDL from oxidation. SUMMARY During inflammation multiple changes in HDL structure occur leading to alterations in HDL function. In the short term, these changes may be beneficial resulting in an increase in cholesterol in peripheral cells to improve host defense and repair but over the long term these changes may increase the risk of atherosclerosis.
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Affiliation(s)
- Kenneth R Feingold
- Metabolism Section, Department of Veterans Affairs Medical Center, University of California San Francisco, San Francisco, California, USA
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Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation in rheumatoid arthritis. Clin Sci (Lond) 2016; 130:1889-99. [DOI: 10.1042/cs20160374] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Accepted: 08/12/2016] [Indexed: 02/04/2023]
Abstract
Anti-paraoxonase 1 (PON1) antibodies could be a potential missing link between oxidative status, inflammation and cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients. Therefore, they could represent an emerging clinical biomarker of CV risk in this condition.
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Associations between disease activity, markers of HDL functionality and arterial stiffness in patients with rheumatoid arthritis. Atherosclerosis 2016; 251:438-444. [DOI: 10.1016/j.atherosclerosis.2016.06.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 06/03/2016] [Accepted: 06/07/2016] [Indexed: 02/04/2023]
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Baysal E, Gulsen S, Aytac I, Celenk F, Ensari N, Taysi S, Binici H, Durucu C, Mumbuc S, Kanlikama M. Oxidative stress in otosclerosis. Redox Rep 2016; 22:235-239. [PMID: 27387094 DOI: 10.1080/13510002.2016.1207920] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
OBJECTIVES Otosclerosis is a disease involving abnormal bone turnover in the human otic capsule that results in hearing loss. Several hypotheses have been suggested for the etiopathogenesis of otosclerosis; however, its etiology remains unclear. METHODS This study evaluated the correlation between otosclerosis and levels of paraoxonase-1 (PON1), arylesterase, total antioxidant status, total oxidant status (TOS), oxidative stress index (OSI), total sulfhydryl (-SH) groups, lipid hydroperoxide, and ceruloplasmin in the serum of otosclerosis patients and healthy subjects with respect to oxidative stress. RESULTS In our study, TOS and OSI levels were higher in the otosclerosis patients than in the controls. The PON1 levels showed that oxidative stress was severe, and as a result, antioxidants were consumed and depleted. DISCUSSION When an imbalance between oxygen free radical production and antioxidative defense mechanisms occurs, reactive oxygen species levels may increase, which in turn may damage cells and tissues through the peroxidation of phospholipid membrane structures. The body initially responds with increased antioxidant production, but if the oxidative stress is severe, decreased antioxidant levels may result. This study reports expression levels of oxidative stress species in otosclerosis patients.
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Affiliation(s)
- Elif Baysal
- a Faculty of Medicine, Otolaryngology Department , Inonu University , Malatya , Turkey
| | | | | | - Fatih Celenk
- d Faculty of Medicine, Otolaryngology Department , Gaziantep University , Gaziantep , Turkey
| | - Nuray Ensari
- e Antalya Education and Research Hospital , Antalya , Turkey
| | - Seyithan Taysi
- f Faculty of Medicine, Biochemistry Department , Gaziantep University , Gaziantep , Turkey
| | - Habib Binici
- g Faculty of Medicine, Otolaryngology Department , Harran University , Sanliurfa , Turkey
| | - Cengiz Durucu
- d Faculty of Medicine, Otolaryngology Department , Gaziantep University , Gaziantep , Turkey
| | - Semih Mumbuc
- d Faculty of Medicine, Otolaryngology Department , Gaziantep University , Gaziantep , Turkey
| | - Muzaffer Kanlikama
- d Faculty of Medicine, Otolaryngology Department , Gaziantep University , Gaziantep , Turkey
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Autoimmune atherosclerosis in 3D: How it develops, how to diagnose and what to do. Autoimmun Rev 2016; 15:756-69. [PMID: 26979271 DOI: 10.1016/j.autrev.2016.03.014] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Accepted: 03/07/2016] [Indexed: 12/11/2022]
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Rodríguez-Carrio J, López-Mejías R, Alperi-López M, López P, Ballina-García FJ, González-Gay MÁ, Suárez A. Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti-High-Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease. Arthritis Rheumatol 2016; 68:1367-76. [DOI: 10.1002/art.39609] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 01/19/2016] [Indexed: 01/06/2023]
Affiliation(s)
| | | | | | | | | | - Miguel Á. González-Gay
- Hospital Universitario Marqués de Valdecilla, Santander, Spain, and Clinical University Hospital of Santiago de Compostela; Santiago de Compostela Spain
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Argani H, Ghorbanihaghjo A, Vatankhahan H, Rashtchizadeh N, Raeisi S, Ilghami H. The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia. SAO PAULO MED J 2016; 134:234-9. [PMID: 27191247 PMCID: PMC10496609 DOI: 10.1590/1516-3180.2015.01702312] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 08/22/2015] [Accepted: 12/23/2015] [Indexed: 12/21/2022] Open
Abstract
CONTEXT AND OBJECTIVE Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.
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Affiliation(s)
- Hassan Argani
- MD. Professor, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Amir Ghorbanihaghjo
- MSc, PhD. Professor, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Hamid Vatankhahan
- MSc. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Nadereh Rashtchizadeh
- MSc, PhD. Professor, Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Sina Raeisi
- MSc. Doctoral Student, Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Hadi Ilghami
- MSc. Doctoral Student, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Ivanišević J, Kotur-Stevuljević J, Stefanović A, Spasić S, Vučinić Mihailović V, Videnović Ivanov J, Jelić-Ivanović Z. Association of serum amyloid A and oxidative stress with paraoxonase 1 in sarcoidosis patients. Eur J Clin Invest 2016; 46:418-24. [PMID: 26919159 DOI: 10.1111/eci.12610] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 02/19/2016] [Indexed: 11/27/2022]
Abstract
BACKGROUND It has been reported that high-density lipoprotein (HDL) particles have anti-inflammatory and antioxidant roles thanks to different enzymes such as paraoxonase 1 (PON1). Under inflammatory and oxidative stress conditions, HDL particles may lose their protective properties. Sarcoidosis is an inflammatory disease characterized by excessive oxidative stress. Serum amyloid A (SAA) is produced in liver and in granulomas, and its concentration increases in inflammatory conditions contributing to increased catabolism of HDL particles. The aim of our study was to determine PON1 activity, SAA concentration and their associations in patients with sarcoidosis. MATERIALS AND METHODS Inflammatory [high-sensitive C-reactive protein (hsCRP), angiotensin-converting enzyme (ACE), SAA], lipid [total cholesterol (TC), HDL-cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG)] oxidative stress status parameters [total oxidant status (TOS), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), sulfhydryl (SH) groups] and PON1 activities were determined in serum of 72 patients with sarcoidosis and 62 healthy subjects. RESULTS HsCRP (P < 0·05), TC, LDL-c, TG, SAA, TOS, MDA and PAB (P < 0·001) were significantly higher, whereas HDL-c, SH groups and PON1 activity (P < 0·001) were significantly lower in patients with sarcoidosis when compared with controls. PON1 showed significant association with SAA, MDA and PAB. It was shown that 71% of decrease in PON1 activity may be explained by increase in TOS, PAB and SAA concentration. CONCLUSIONS We found decreased PON1 activity and increased SAA concentration in patients with sarcoidosis. Inflammatory condition presented by high SAA was implicated in impaired HDL functionality evident through dysregulated PON1 activity. Excessive oxidative stress was also involved in dysregulation of PON1 activity.
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Affiliation(s)
- Jasmina Ivanišević
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Jelena Kotur-Stevuljević
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Stefanović
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Slavica Spasić
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | | | | | - Zorana Jelić-Ivanović
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
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Prüfer N, Kleuser B, van der Giet M. The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality. Biol Chem 2016; 396:573-83. [PMID: 25252751 DOI: 10.1515/hsz-2014-0192] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2014] [Accepted: 09/23/2014] [Indexed: 11/15/2022]
Abstract
The high-density lipoprotein (HDL) is one of the most important endogenous cardiovascular protective markers. HDL is an attractive target in the search for new pharmaceutical therapies and in the prevention of cardiovascular events. Some of HDL's anti-atherogenic properties are related to the signaling molecule sphingosine-1-phosphate (S1P), which plays an important role in vascular homeostasis. However, for different patient populations it seems more complicated. Significant changes in HDL's protective potency are reduced under pathologic conditions and HDL might even serve as a proatherogenic particle. Under uremic conditions especially there is a change in the compounds associated with HDL. S1P is reduced and acute phase proteins such as serum amyloid A (SAA) are found to be elevated in HDL. The conversion of HDL in inflammation changes the functional properties of HDL. High amounts of SAA are associated with the occurrence of cardiovascular diseases such as atherosclerosis. SAA has potent pro-atherogenic properties, which may have impact on HDL's biological functions, including cholesterol efflux capacity, antioxidative and anti-inflammatory activities. This review focuses on two molecules that affect the functionality of HDL. The balance between functional and dysfunctional HDL is disturbed after the loss of the protective sphingolipid molecule S1P and the accumulation of the acute-phase protein SAA. This review also summarizes the biological activities of lipid-free and lipid-bound SAA and its impact on HDL function.
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Kim MJ, Park M, Kim DW, Shin MJ, Son O, Jo HS, Yeo HJ, Cho SB, Park JH, Lee CH, Kim DS, Kwon OS, Kim J, Han KH, Park J, Eum WS, Choi SY. Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model. Biomaterials 2015; 64:45-56. [DOI: 10.1016/j.biomaterials.2015.06.015] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Revised: 06/09/2015] [Accepted: 06/11/2015] [Indexed: 01/01/2023]
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Paired measurement of serum amyloid A (SAA) and paraoxonase 1 (PON1) as useful markers in breast cancer recurrence. Clin Biochem 2015; 48:1181-3. [PMID: 26188919 DOI: 10.1016/j.clinbiochem.2015.07.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 07/07/2015] [Accepted: 07/13/2015] [Indexed: 11/22/2022]
Abstract
OBJECTIVES Paraoxonase 1 (PON1) and serum amyloid A (SAA) are carried by HDL. In case of inflammation, SAA and PON1 tend to change in opposite direction. In this study we determined if inflammation leads to altered PON1 activity using three different substrate hydrolysis rates, paraoxonase (PON), arylesterase (ARE) and lactonase (LAC) in breast cancer recurrence. DESIGN AND METHODS 49 patients with a recurrence of breast cancer were analyzed for SAA, CRP, lipids, oxidized LDL, PON, ARE and LAC. Distribution of PON1 activities across the quartiles of CRP and SAA were compared by the Kruskal Wallis test. Non-parametric estimates of the survivor function were computed with Kaplan-Meier method. The association of SAA and ARE with short term death was assessed by logistic regression models. RESULTS HDL and ARE decrease significantly across the quartiles of CRP. No significant differences were observed across SAA quartiles. The survival time was significantly related to the level of SAA (log rank: p<0.001) as well as the level of ARE (log rank: p=0.039). SAA and ARE were independently related to survival time below one year. CONCLUSIONS PON1 does not seem to be directly affected by SAA, for any of the tested substrates, PON, ARE and LAC. The combined measurement of SAA and ARE could be a useful tool in this clinical situation, since they are independently related to short term death.
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El-Banna H, Jiman-Fatani A. Anti-cyclic citrullinated peptide antibodies and paraoxonase-1 polymorphism in rheumatoid arthritis. BMC Musculoskelet Disord 2014; 15:379. [PMID: 25406539 PMCID: PMC4247608 DOI: 10.1186/1471-2474-15-379] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 11/05/2014] [Indexed: 01/11/2023] Open
Abstract
Background Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease, with a worldwide prevalence of 0.5% to 1%. Anti-cyclic citrullinated peptide antibody (anti-CCP-2 Ab) is a marker of choice for diagnosing early and late RA. Anti-oxidant enzymes activity decreases in RA patients. Till now, the relationship between the rheumatoid factor (RF) and anti-CCP-2 Ab, anti-oxidant activity and polymorphism of paraoxenase-1 (PON-1) 192 Q/R in patients with RA has not been investigated. In this study, we aimed to determine the serum level of RF and anti-CCP-2 Ab, PON-1 activity and 192 Q/R polymorphism and arylesterase (ARE) activity in patients with RA. Also, we studied RA markers in different genotypes of PON-1 of RA patients. Methods A total of 120 RA patients and 90 healthy persons were subjected to full clinical examinations and routine laboratory tests. PON-1 and ARE activities were determined using an enzymatic spectrophotometric method. PON-1 192 gene polymorphism was determined using polymerase chain reaction based restriction fragment analysis. RF was measured by immunoturbidimetry method and anti-CCP-2 Ab was assayed by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using SPSS for windows 20.0. Results The sensitivity and specificity of anti-CCP-2 Ab for the diagnosis of RA were 76.2% and 100% respectively. PON-1 and ARE activities were statistically lower (P <0.001) in the RA group compared to the control group. A negative correlation between RF and anti-CCP-2 Ab levels and PON-1 and ARE activities was found. No significant difference in the genotype distribution between RA patients and healthy persons was detected. RF and anti-CCP-2 Ab levels were higher in RA patients carried RR genotype than in those carried QQ genotype. Conclusion High RF and anti-CCP-2 antibody serum levels were found to be associated with decreased PON-1 and ARE activities with no correlation between PON-1 polymorphism and serum levels of RF and anti-CCP-2 Ab in patients with RA. These results may indicate an implication between antioxidant enzymes activity and serum levels of RF and anti-CCP-2 Ab.
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Affiliation(s)
| | - Asif Jiman-Fatani
- Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
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Kerekes G, Nurmohamed MT, González-Gay MA, Seres I, Paragh G, Kardos Z, Baráth Z, Tamási L, Soltész P, Szekanecz Z. Rheumatoid arthritis and metabolic syndrome. Nat Rev Rheumatol 2014; 10:691-6. [DOI: 10.1038/nrrheum.2014.121] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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