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Gastoł J, Paszek E, Bryk-Wiązania A, Matejko B, Undas A. Good metabolic control is associated with decreased circulating factor VIIa- antithrombin complexes in type 2 diabetes: a cross-sectional study. Cardiovasc Diabetol 2024; 23:398. [PMID: 39501309 PMCID: PMC11536800 DOI: 10.1186/s12933-024-02480-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 10/21/2024] [Indexed: 11/09/2024] Open
Abstract
BACKGROUND Diabetes is associated with a prothrombotic state that contributes to cardiovascular (CV) events in type 2 diabetes (T2DM). Activated factor VII (FVIIa)- antithrombin (AT) complexes are indicative of tissue factor (TF) exposure and have been associated with thromboembolic risk in coronary artery disease. To our knowledge there have been no reports on FVIIa-AT complexes in T2DM, therefore we assessed factors that determine FVIIa-AT complexes in this disease and the impact of higher complexes on a prothrombotic state. METHODS In 108 T2DM patients (mean age 63.8 years, 52.8% men, median HbA1c of 6.9 [interquartile range 6.1-8.2] %) and 83 age- and sex-matched non-diabetic subjects, we measured FVIIa-AT complexes. Metabolic control of T2DM involved fasting glucose, glycated hemoglobin (HbA1c), albumin/creatinine ratio (ACR), and lipid levels. To characterize a prothrombotic state, we determined thrombin generation parameters, fibrinolysis markers, and plasma fibrin clot properties. RESULTS FVII-AT complexes in T2DM patients were similar to controls (73.6 [59.4-91.7] vs. 79.6 [59.2-97.1]pM, respectively, p = 0.30). The T2DM patients with FVIIa-AT in the top vs. the bottom quartile had a larger prevalence of active smoking and insulin use, along with higher fasting glucose (+ 36.4%), HbA1c (+ 27.4%), ACR (+ 72.8%), total cholesterol (+ 34.5%), and LDL-cholesterol (+ 80%). FVIIa-AT complexes showed no associations with in vitro thrombin generation potential, plasma fibrin clot properties, or fibrinolysis variables. On multivariable analysis HbA1c, ACR, and total cholesterol remained independently associated with FVIIa-AT complexes in T2DM. CONCLUSIONS This is the first study to show that in T2DM higher FVIIa-AT complexes are associated with markers of dyslipidemia and glycemia control, indicating that TF-induced coagulation activation could be suppressed by achieving treatment targets.
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Affiliation(s)
- Joanna Gastoł
- Metabolic Diseases and Diabetology Clinical Department, University Hospital, Kraków, Poland
- Department of Metabolic Diseases, Jagiellonian University Medical College, Kraków, Poland
| | - Elżbieta Paszek
- Clinical Department of Interventional Cardiology, John Paul II Hospital, Kraków, Poland
- Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St, 31-202, Kraków, Poland
| | - Agata Bryk-Wiązania
- Department of Endocrinology, Jagiellonian University Medical College, Kraków, Poland
- Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Kraków, Poland
| | - Bartłomiej Matejko
- Metabolic Diseases and Diabetology Clinical Department, University Hospital, Kraków, Poland
- Department of Metabolic Diseases, Jagiellonian University Medical College, Kraków, Poland
| | - Anetta Undas
- Department of Thromboembolic Disorders, Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St, 31-202, Kraków, Poland.
- Cracow Center for Medical Research and Technology, John Paul II Hospital, Kraków, Poland.
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Zhang L, Xiong Y, Zhang J, Feng Y, Xu A. Systematic proteome-wide Mendelian randomization using the human plasma proteome to identify therapeutic targets for lung adenocarcinoma. J Transl Med 2024; 22:330. [PMID: 38576019 PMCID: PMC10993587 DOI: 10.1186/s12967-024-04919-z] [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: 11/07/2023] [Accepted: 01/21/2024] [Indexed: 04/06/2024] Open
Abstract
BACKGROUND Lung adenocarcinoma (LUAD) is the predominant histological subtype of lung cancer and the leading cause of cancer-related mortality. Identifying effective drug targets is crucial for advancing LUAD treatment strategies. METHODS This study employed proteome-wide Mendelian randomization (MR) and colocalization analyses. We collected data on 1394 plasma proteins from a protein quantitative trait loci (pQTL) study involving 4907 individuals. Genetic associations with LUAD were derived from the Transdisciplinary Research in Cancer of the Lung (TRICL) study, including 11,245 cases and 54,619 controls. We integrated pQTL and LUAD genome-wide association studies (GWASs) data to identify candidate proteins. MR utilizes single nucleotide polymorphisms (SNPs) as genetic instruments to estimate the causal effect of exposure on outcome, while Bayesian colocalization analysis determines the probability of shared causal genetic variants between traits. Our study applied these methods to assess causality between plasma proteins and LUAD. Furthermore, we employed a two-step MR to quantify the proportion of risk factors mediated by proteins on LUAD. Finally, protein-protein interaction (PPI) analysis elucidated potential links between proteins and current LUAD medications. RESULTS We identified nine plasma proteins significantly associated with LUAD. Increased levels of ALAD, FLT1, ICAM5, and VWC2 exhibited protective effects, with odds ratios of 0.79 (95% CI 0.72-0.87), 0.39 (95% CI 0.28-0.55), 0.91 (95% CI 0.72-0.87), and 0.85 (95% CI 0.79-0.92), respectively. Conversely, MDGA2 (OR, 1.13; 95% CI 1.08-1.19), NTM (OR, 1.12; 95% CI 1.09-1.16), PMM2 (OR, 1.35; 95% CI 1.18-1.53), RNASET2 (OR, 1.15; 95% CI 1.08-1.21), and TFPI (OR, 4.58; 95% CI 3.02-6.94) increased LUAD risk. Notably, none of the nine proteins showed evidence of reverse causality. Bayesian colocalization indicated that RNASET2, TFPI, and VWC2 shared the same variant with LUAD. Furthermore, NTM and FLT1 demonstrated interactions with targets of current LUAD medications. Additionally, FLT1 and TFPI are currently under evaluation as therapeutic targets, while NTM, RNASET2, and VWC2 are potentially druggable. These findings shed light on LUAD pathogenesis, highlighting the tumor-promoting effects of RNASET2, TFPI, and NTM, along with the protective effects of VWC2 and FLT1, providing a significant biological foundation for future LUAD therapeutic targets. CONCLUSIONS Our proteome-wide MR analysis highlighted RNASET2, TFPI, VWC2, NTM, and FLT1 as potential drug targets for further clinical investigation in LUAD. However, the specific mechanisms by which these proteins influence LUAD remain elusive. Targeting these proteins in drug development holds the potential for successful clinical trials, providing a pathway to prioritize and reduce costs in LUAD therapeutics.
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Affiliation(s)
- Long Zhang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yajun Xiong
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jie Zhang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yuying Feng
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Aiguo Xu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
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Balasenthil S, Liu S, Dai J, Bamlet WR, Petersen G, Chari ST, Maitra A, Chen N, Sen S, McNeill Killary A. Blood-based Migration Signature Biomarker Panel Discriminates Early Stage New Onset Diabetes related Pancreatic Ductal Adenocarcinoma from Type 2 Diabetes. Clin Chim Acta 2023; 551:117567. [PMID: 37774897 DOI: 10.1016/j.cca.2023.117567] [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: 07/20/2023] [Revised: 09/19/2023] [Accepted: 09/26/2023] [Indexed: 10/01/2023]
Abstract
BACKGROUND AND AIMS While type 2 diabetes is a well-known risk factor for pancreatic ductal adenocarcinoma (PDAC), PDAC-induced new-onset diabetes (PDAC-NOD) is a manifestation of underlying PDAC. In this study, we sought to identify potential blood-based biomarkers for distinguishing PDAC-NOD from type 2 diabetes (T2DM) without PDAC. MATERIALS AND METHODS By ELISA analysis, a migration signature biomarker panel comprising tissue factor pathway inhibitor (TFPI), tenascin C (TNC-FNIII-C) and CA 19-9 was analyzed in plasma samples from 50 PDAC-NOD and 50 T2DM controls. RESULTS Both TFPI (area under the curve (AUC) 0.71) and TNC-FNIII-C (AUC 0.69) outperformed CA 19-9 (AUC 0.60) in distinguishing all stages of PDAC-NOD from T2DM controls. The combined panel showed an AUC of 0.82 (95% CI = 0.73-0.90) (p = 0.002). In the PDAC-NOD early stage II samples, the three biomarkers had an AUC of 0.84 (95% CI = 0.73-0.93) vs CA 19-9, AUC = 0.60, (95% CI = 0.45-0.73), which also improved significance (p = 0.0123). CONCLUSION The migration signature panel adds significantly to CA 19-9 to discriminate PDAC-NOD from T2DM controls and warrants further validation for high-risk group stratification.
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Affiliation(s)
- Seetharaman Balasenthil
- Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
| | - Suyu Liu
- Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
| | - Jianliang Dai
- Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
| | - William R Bamlet
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Gloria Petersen
- Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA
| | - Suresh T Chari
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
| | - Anirban Maitra
- Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA; Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
| | - Nanyue Chen
- Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
| | - Subrata Sen
- Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
| | - Ann McNeill Killary
- Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
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Okue S, Yaguchi M, Miura A, Ozaki-Masuzawa Y, Hosono T, Seki T. The garlic-derived organosulfur compound diallyl trisulphide suppresses tissue factor function. Food Funct 2022; 13:1246-1255. [PMID: 35022635 DOI: 10.1039/d1fo02206g] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Tissue factor (TF) is a critical initiator of extrinsic coagulation that sometimes causes thromboembolism. Diallyl trisulphide (DATS) is a secondary metabolite of allicin generated in crushed garlic, with various pharmacological effects. This study aimed to clarify the effect of DATS on the extrinsic coagulation elicited by TF and arteriosclerosis. TF activity was measured using a clotting assay in TF-expressing HL60 cells. DATS inhibited TF activity in a dose-dependent manner. TF expression in TNF-α-stimulated human umbilical vein endothelial cells was examined using real-time PCR and western blotting. DATS inhibited TF mRNA and protein expression induced by TNF-α via inhibition of JNK signalling. The effect of DATS on arteriosclerosis was also examined in apolipoprotein E-deficient mice. DATS administration in these mice tended to decrease atherosclerotic lesion size. These results strongly suggest that DATS prevents thromboembolism triggered by atherosclerosis via the inhibition of plaque formation and TF function.
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Affiliation(s)
- Sachiko Okue
- Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan.
| | - Manami Yaguchi
- Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan.
| | - Atsushi Miura
- Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan.
| | - Yori Ozaki-Masuzawa
- Department of Chemistry and Life Science, Collage of Bioresource Sciences, Nihon University, Kanagawa, Japan
| | - Takashi Hosono
- Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan. .,Department of Chemistry and Life Science, Collage of Bioresource Sciences, Nihon University, Kanagawa, Japan
| | - Taiichiro Seki
- Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan. .,Department of Chemistry and Life Science, Collage of Bioresource Sciences, Nihon University, Kanagawa, Japan
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Tchaikovski SN, Thomassen MCLGD, Stickeler E, Bremme K, Rosing J. Resistance to activated protein C and impaired TFPI activity in women with previous hormone-induced venous thromboembolism. Thromb Res 2021; 207:143-149. [PMID: 34634502 DOI: 10.1016/j.thromres.2021.09.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 09/07/2021] [Accepted: 09/25/2021] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Hormonal contraception is a well-known risk factor for venous thromboembolism (VTE). APC resistance and impaired functions of protein S and TFPI are thought to play an important role in the pathogenesis of hormone-related VTE. It is unknown, whether women, who develop VTE during hormonal contraception possess a vulnerability in these pathways, making them susceptible to thrombosis. MATERIALS AND METHODS Plasma samples were obtained from 57 premenopausal women in average 15.3 years after hormone-associated VTE and from 31 healthy controls. Thrombin generation at high tissue factor (TF) in the absence and in the presence of activated protein C (APC) and at low TF without and with inhibiting anti-protein S- and anti-TFPI-antibodies was measured via calibrated automated thrombography. RESULTS Women with previous hormone-related thrombosis had higher thrombin generation at low TF, higher APC resistance, protein S- and TFPI ratios, differences: 219.9 nM IIa.min (95%CI:90.4 to 349.3); 1.88 (95%CI:0.71 to 3.05); 0.13 (95%CI:0.01 to 0.26) and 0.19 (95%CI:0.08 to 0.30), respectively. Thrombin generation at high TF without APC did not differ between the groups. Smoking decreased thrombin generation at low TF by -222.6 nM IIa.min (95%CI: -381.1 to -64.1), the APC sensitivity ratio by -2.20 (95%CI: -3.63 to -0.77) and the TFPI ratio by -0.16 (95%CI: -0.29 to -0.03), but did not influence thrombin generation at high TF. DISCUSSION We demonstrated impairment of the protein S/TFPI system and increased APC resistance in women with previous hormone-induced VTE. Smoking decreased thrombin generation at assay conditions, dependent on the function of the TFPI system.
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Affiliation(s)
- S N Tchaikovski
- University Clinic for Gynaecology and Obstetrics, RWTH Aachen, Germany; University Clinic for Gynaecology and Obstetrics, Otto von Guericke University Magdeburg, Germany.
| | - M C L G D Thomassen
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
| | - E Stickeler
- University Clinic for Gynaecology and Obstetrics, RWTH Aachen, Germany
| | - K Bremme
- Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - J Rosing
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
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Sobczak AIS, Stewart AJ. Coagulatory Defects in Type-1 and Type-2 Diabetes. Int J Mol Sci 2019; 20:E6345. [PMID: 31888259 PMCID: PMC6940903 DOI: 10.3390/ijms20246345] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 12/06/2019] [Accepted: 12/12/2019] [Indexed: 12/16/2022] Open
Abstract
Diabetes (both type-1 and type-2) affects millions of individuals worldwide. A major cause of death for individuals with diabetes is cardiovascular diseases, in part since both types of diabetes lead to physiological changes that affect haemostasis. Those changes include altered concentrations of coagulatory proteins, hyper-activation of platelets, changes in metal ion homeostasis, alterations in lipid metabolism (leading to lipotoxicity in the heart and atherosclerosis), the presence of pro-coagulatory microparticles and endothelial dysfunction. In this review, we explore the different mechanisms by which diabetes leads to an increased risk of developing coagulatory disorders and how this differs between type-1 and type-2 diabetes.
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Affiliation(s)
| | - Alan J. Stewart
- Medical and Biological Sciences Building, School of Medicine, University of St Andrews, St Andrews KY16 9TF, UK;
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Compression socks and the effects on coagulation and fibrinolytic activation during marathon running. Eur J Appl Physiol 2018; 118:2171-2177. [PMID: 30043183 DOI: 10.1007/s00421-018-3929-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Accepted: 06/30/2018] [Indexed: 10/28/2022]
Abstract
PURPOSE Compression socks are frequently used in the treatment and prevention of lower-limb pathologies; however, when combined with endurance-based exercise, the impact of compression socks on haemostatic activation remains unclear. OBJECTIVES To investigate the effect of wearing compression socks on coagulation and fibrinolysis following a marathon. METHODS Sixty-seven participants [43 males (mean ± SD: age: 46.7 ± 10.3 year) and 24 females (age: 40.0 ± 11.0 year)] were allocated into a compression (SOCK, n = 34) or control (CONTROL, n = 33) group. Venous blood samples were obtained 24 h prior to and immediately POST-marathon, and were analyzed for thrombin-anti-thrombin complex (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), and D-Dimer. RESULTS Compression significantly attenuated the post-exercise increase in D-Dimer compared to the control group [median (range) SOCK: + 9.02 (- 0.34 to 60.7) ng/mL, CONTROL: + 25.48 (0.95-73.24) ng/mL]. TF increased following the marathon run [median (range), SOCK: + 1.19 (- 7.47 to 9.11) pg/mL, CONTROL: + 3.47 (- 5.01 to 38.56) pg/mL] in all runners. No significant post-exercise changes were observed for TAT and TFPI. CONCLUSIONS While activation of coagulation and fibrinolysis was apparent in all runners POST-marathon, wearing compression socks was shown to reduce fibrinolytic activity, as demonstrated by lower D-Dimer concentrations. Compression may reduce exercise-associated haemostatic activation when completing prolonged exercise.
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Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population. J Thromb Thrombolysis 2018; 46:88-94. [DOI: 10.1007/s11239-018-1666-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Zhao Y, Yu Y, Shi M, Yang X, Li X, Jiang F, Chen Y, Tian X. Association study to evaluate TFPI gene in CAD in Han Chinese. BMC Cardiovasc Disord 2017; 17:188. [PMID: 28716011 PMCID: PMC5514508 DOI: 10.1186/s12872-017-0626-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 07/12/2017] [Indexed: 12/11/2022] Open
Abstract
Background Tissue factor pathway inhibitor (TFPI) is the main physiological inhibitor of TF-induced blood coagulation process, and may play essential roles in the pathogenesis of major adverse cardiac events. This study was designed to determine whether the variation of TFPI was related with coronary artery disease (CAD) in the Han Chinese populations. Methods A total of 1271 patients with coronary atherosclerosis and 1287 normal individuals from northern China were enrolled in the present study. Four tagging single-nucleotide polymorphisms (SNPs) (rs7586970, rs6434222, rs10153820 and rs8176528) from TFPI were selected and genotyped by direct sequencing. And the genotypes of the above SNPs were determined in all these participants. Results In the populations from Beijing and Harbin, no significant case-control differences in the frequencies of TFPI polymorphism (rs10153820 and rs8176528) were observed between CAD patients and controls. Meanwhile, two SNPs of TFPI (rs7586970 and rs6434222) were found to be associated with CAD in both groups. In stratified analyses based on gender, smoking, hypertension, diabetes mellitus and hyperlipidemia, we further determined that the investigated genetic variations of the TFPI genes seemed to be related with diabetes mellitus in CAD patients. Conclusions Genetic variations of the TFPI genes seem to be related with CAD, which likely cooperate with metabolic risk factor (diabetes mellitus) and play critical roles in the pathogenesis of coronary artery disease.
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Affiliation(s)
- Ying Zhao
- Department of Geriatrics, Jinan Military General Hospital, Jinan, 250031, China
| | - Yanbo Yu
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, 250012, China
| | - Maowei Shi
- Department of Geriatrics, Jinan Military General Hospital, Jinan, 250031, China
| | - Xi Yang
- Department of Human Population Genetics, Institute of Molecular Medicine, Peking University, Beijing, 100871, China
| | - Xueqi Li
- Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Feng Jiang
- Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Yundai Chen
- Department of Cardiology, Chinese PLA General Hospital, Beijing, 100853, China.
| | - Xiaoli Tian
- Department of Human Population Genetics, Institute of Molecular Medicine, Peking University, Beijing, 100871, China.
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Tissue factor levels in type 2 diabetes mellitus. Inflamm Res 2017; 66:365-368. [PMID: 28246677 DOI: 10.1007/s00011-017-1030-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 02/15/2017] [Accepted: 02/17/2017] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Type 2 diabetes mellitus is a pandemic associated with disturbance in haemostasis that could contribute to the development of diabetic vascular disease and accelerated atherosclerosis. In this population, hypercoagulation is prevalent, as well as pathological changes to erythrocytes. This is mainly due to upregulated circulating inflammatory markers. MATERIALS AND METHODS Here we looked at tissue factor (TF) levels using ELISA, in a sample of diabetics, with and without cardiovascular complications. Diabetic subjects were recruited from the diabetic clinic at Steve Biko Academic Hospital, Pretoria, South Africa. 20 diabetics with cardiovascular disease and 22 without were enrolled to participate. RESULTS AND CONCLUSION TF levels were significantly elevated in both diabetic groups when compared to the controls. We suggest that pathologic plasma TF activity, as marker of increased propensity of clot pathology, should be investigated. Agents that might lower TF levels might also possibly lower thrombotic complications.
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Uchimura I, Kaibara M, Nagasawa M, Hayashi Y. Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry. Biorheology 2016; 53:209-219. [PMID: 27858671 PMCID: PMC5389046 DOI: 10.3233/bir-16107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. OBJECTIVE The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). METHODS Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. RESULTS The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. CONCLUSIONS Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group.
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Affiliation(s)
- Isao Uchimura
- Department of Endocrinology and Metabolism, Tokyo Medical and Dental University, Tokyo, Japan
| | - Makoto Kaibara
- RIKEN (The Institute of Physical and Chemical Research), Wako, Saitama, Japan
| | - Masayuki Nagasawa
- Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Pediatrics, Musashino Red Cross Hospital, Musashino-city, Tokyo, Japan
| | - Yoshihito Hayashi
- LE Development Department, R&D Division, Medical Business Unit, Imaging Products & Solutions Sector, Sony Corporation, Tokyo, Japan
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Ruszkowska-Ciastek B, Sokup A, Wernik T, Rhone P, Góralczyk K, Bielawski K, Fijałkowska A, Nowakowska A, Rhone E, Rość D. Low-grade risk of hypercoagulable state in patients suffering from diabetes mellitus type 2. J Zhejiang Univ Sci B 2016; 16:788-95. [PMID: 26365121 DOI: 10.1631/jzus.b1500066] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVE Diabetes, including type 1 and type 2, is associated with the hypercoagulable state. The aim of this study is to evaluate the concentration of selected hemostatic parameters and vascular endothelial growth factor-A (VEGF-A) in diabetic subjects. METHODS The study was conducted in 62 patients with diabetes. Group I consisted of 27 patients having uncontrolled diabetes with microalbuminuria and Group II included 35 well-controlled diabetic patients. The control group was made up of 25 healthy volunteers. In the citrate plasma, the concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombin-antithrombin (TAT) complexes, and D-dimer were assayed. Serum concentrations of VEGF-A, lipid profile, creatinine, and plasma fasting glucose were measured and in the versene plasma the concentration of HbA1c was determined. RESULTS In the patients with uncontrolled diabetes, higher concentrations of TF, TFPI, and VEGF-A were observed, as compared with the well-controlled diabetics group and the control group. A significantly lower activity of antiplasmin was reported in patients from Group I as compared with the control group. In Group I, using the multivariate regression analysis, the glomerular filtration rate was independently associated with VEGF-A and dependently associated with total cholesterol. CONCLUSIONS The study showed higher concentrations of TF and TFPI in the patients with uncontrolled diabetes with microalbuminuria, which is associated with rapid neutralization of the thrombin formation, since TFPI inhibits the complex of TF/VIIa/Ca(2+). The manifestation of the above suggestions is the correct TAT complexes and D-dimer, which indicates a low grade of prothrombotic risk in this group of patients, but a higher risk of vascular complications.
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Affiliation(s)
- Barbara Ruszkowska-Ciastek
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland
| | - Alina Sokup
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland
| | - Tomasz Wernik
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland
| | - Piotr Rhone
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland
| | - Krzysztof Góralczyk
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland
| | - Kornel Bielawski
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland
| | - Agata Fijałkowska
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland
| | - Aleksandra Nowakowska
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland
| | - Elżbieta Rhone
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland
| | - Danuta Rość
- Department of Pathophysiology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Bydgoszcz PL 85-094, Poland
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Arkova OV, Ponomarenko MP, Rasskazov DA, Drachkova IA, Arshinova TV, Ponomarenko PM, Savinkova LK, Kolchanov NA. Obesity-related known and candidate SNP markers can significantly change affinity of TATA-binding protein for human gene promoters. BMC Genomics 2015; 16 Suppl 13:S5. [PMID: 26694100 PMCID: PMC4686794 DOI: 10.1186/1471-2164-16-s13-s5] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Obesity affects quality of life and life expectancy and is associated with cardiovascular disorders, cancer, diabetes, reproductive disorders in women, prostate diseases in men, and congenital anomalies in children. The use of single nucleotide polymorphism (SNP) markers of diseases and drug responses (i.e., significant differences of personal genomes of patients from the reference human genome) can help physicians to improve treatment. Clinical research can validate SNP markers via genotyping of patients and demonstration that SNP alleles are significantly more frequent in patients than in healthy people. The search for biomedical SNP markers of interest can be accelerated by computer-based analysis of hundreds of millions of SNPs in the 1000 Genomes project because of selection of the most meaningful candidate SNP markers and elimination of neutral SNPs. RESULTS We cross-validated the output of two computer-based methods: DNA sequence analysis using Web service SNP_TATA_Comparator and keyword search for articles on comorbidities of obesity. Near the sites binding to TATA-binding protein (TBP) in human gene promoters, we found 22 obesity-related candidate SNP markers, including rs10895068 (male breast cancer in obesity); rs35036378 (reduced risk of obesity after ovariectomy); rs201739205 (reduced risk of obesity-related cancers due to weight loss by diet/exercise in obese postmenopausal women); rs183433761 (obesity resistance during a high-fat diet); rs367732974 and rs549591993 (both: cardiovascular complications in obese patients with type 2 diabetes mellitus); rs200487063 and rs34104384 (both: obesity-caused hypertension); rs35518301, rs72661131, and rs562962093 (all: obesity); and rs397509430, rs33980857, rs34598529, rs33931746, rs33981098, rs34500389, rs63750953, rs281864525, rs35518301, and rs34166473 (all: chronic inflammation in comorbidities of obesity). Using an electrophoretic mobility shift assay under nonequilibrium conditions, we empirically validated the statistical significance (α < 0.00025) of the differences in TBP affinity values between the minor and ancestral alleles of 4 out of the 22 SNPs: rs200487063, rs201381696, rs34104384, and rs183433761. We also measured half-life (t1/2), Gibbs free energy change (ΔG), and the association and dissociation rate constants, ka and kd, of the TBP-DNA complex for these SNPs. CONCLUSIONS Validation of the 22 candidate SNP markers by proper clinical protocols appears to have a strong rationale and may advance postgenomic predictive preventive personalized medicine.
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Affiliation(s)
- Olga V Arkova
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentyeva Avenue, Novosibirsk 630090, Russia
| | - Mikhail P Ponomarenko
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentyeva Avenue, Novosibirsk 630090, Russia
- Novosibirsk State University, 2 Pirogova Street, Novosibirsk 630090, Russia
- Laboratory of Evolutionary Bioinformatics and Theoretical Genetics, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentyev Avenue, Novosibirsk 630090, Russia
| | - Dmitry A Rasskazov
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentyeva Avenue, Novosibirsk 630090, Russia
| | - Irina A Drachkova
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentyeva Avenue, Novosibirsk 630090, Russia
| | - Tatjana V Arshinova
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentyeva Avenue, Novosibirsk 630090, Russia
| | - Petr M Ponomarenko
- Children's Hospital Los Angeles, 4640 Hollywood Boulevard, University of Southern California, Los Angeles, CA 90027, USA
| | - Ludmila K Savinkova
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentyeva Avenue, Novosibirsk 630090, Russia
| | - Nikolay A Kolchanov
- Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 10 Lavrentyeva Avenue, Novosibirsk 630090, Russia
- Novosibirsk State University, 2 Pirogova Street, Novosibirsk 630090, Russia
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Kubisz P, Stančiaková L, Staško J, Galajda P, Mokáň M. Endothelial and platelet markers in diabetes mellitus type 2. World J Diabetes 2015; 6:423-431. [PMID: 25897353 PMCID: PMC4398899 DOI: 10.4239/wjd.v6.i3.423] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Revised: 12/22/2014] [Accepted: 02/02/2015] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is an extremely common disorder which carries a risk of vascular impairment. DM type 2 (DM2) can be characterized by the dysfunction of haemostasis manifesting by stimulated coagulation process, disorder of platelet function and decreased fibrinolytic activity. These all are the reasons why DM2 is the most common acquired thrombophilia. Endothelial dysfunction along with platelet hyperactivity are unquestionably involved in the hyperactivation of platelets and clotting factors in DM. As a natural consequence of continuous investigation, many markers of endothelial dysfunction and diabetic thrombocytopathy have been identified and considered for implementation in clinical practice. Endothelial function can be assessed by the evaluation of endothelial markers, circulating molecules synthesised in various amounts by the endothelium. These markers precede the signs of evident microangiopathy. Platelets have an ethiopathogenic relation to the microangiopathy in DM. Their increased activity was confirmed in both types of DM. Predictors of endothelial and platelet disorder could improve the screening of individuals at increased risk, thus leading to the early diagnosis, appropriate treatment, as well as to the effective prevention of the complications of DM2. In the article we deal with the mechanisms involved in the pathogenesis of endothelial and platelet functional abnormalities, endothelial and platelet markers of DM2 considered for implementation in clinical practice and possibilities of their detection.
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Peripheral blood mononuclear cell gene expression profile in obese boys who followed a moderate energy-restricted diet: differences between high and low responders at baseline and after the intervention. Br J Nutr 2014; 113:331-42. [DOI: 10.1017/s0007114514003584] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
The present study analyses the gene expression profile of peripheral blood mononuclear cells (PBMC) from obese boys. The aims of the present study were to identify baseline differences between low responders (LR) and high responders (HR) after 10 weeks of a moderate energy-restricted dietary intervention, and to compare the gene expression profile between the baseline and the endpoint of the nutritional intervention. Spanish obese boys (age 10–14 years) were advised to follow a 10-week moderate energy-restricted diet. Participants were classified into two groups based on the association between the response to the nutritional intervention and the changes in BMI standard deviation score (BMI-SDS): HR group (n 6), who had a more decreased BMI-SDS; LR group (n 6), who either maintained or had an even increased BMI-SDS. The expression of 28 869 genes was analysed in PBMC from both groups at baseline and after the nutritional intervention, using the Affymetrix Human Gene 1.1 ST 24-Array plate microarray. At baseline, the HR group showed a lower expression of inflammation and immune response-related pathways, which suggests that the LR group could have a more developed pro-inflammatory phenotype. Concomitantly, LEPR and SIRPB1 genes were highly expressed in the LR group, indicating a tendency towards an impaired immune response and leptin resistance. Moreover, the moderate energy-restricted diet was able to down-regulate the inflammatory ‘mitogen-activated protein kinase signalling pathway’ in the HR group, as well as some inflammatory genes (AREG and TNFAIP3). The present study confirms that changes in the gene expression profile of PBMC in obese boys may help to understand the weight-loss response. However, further research is required to confirm these findings.
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Korish AA, Abdel Gader AGM, Alhaider AA. Camel milk ameliorates the coagulopathy in streptozotocin diabetic rat model. INT J DAIRY TECHNOL 2014. [DOI: 10.1111/1471-0307.12168] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Aida A Korish
- Department of Physiology (29) College of Medicine and King Khalid University Hospital King Saud University PO Box 2925 11461 Riyadh Saudi Arabia
| | - Abdel Galil M Abdel Gader
- Department of Physiology (29) College of Medicine and King Khalid University Hospital King Saud University PO Box 2925 11461 Riyadh Saudi Arabia
| | - Abdulqader A Alhaider
- Department of Physiology (29) College of Medicine and King Khalid University Hospital King Saud University PO Box 2925 11461 Riyadh Saudi Arabia
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Dayer MR, Mard-Soltani M, Dayer MS, Alavi SMR. Causality relationships between coagulation factors in type 2 diabetes mellitus: path analysis approach. Med J Islam Repub Iran 2014; 28:59. [PMID: 25405125 PMCID: PMC4219888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2013] [Accepted: 12/17/2013] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Type 2 diabetic mellitus patients are amongst the most susceptible groups to vascular abnormalities, which predominantly lead to myocardial disease. The hypercoagulable state has been widely studied by researchers as being the major suspicious mechanism facilitating the consecutive chain of molecular events leading to these complications. However, there is no consensus on the definition of the hypercoagulable state with respect to coagulation quantities, their interrelations and basic factor(s) initiating this pathogenic event, by which the prognosis of myocardial complications could be determined. METHODS Path analysis was used to study the interactions between coagulation factors as well as other factors beyond coagulation factors in relation with pathogenic events in both diabetics and healthy subjects. In the present work, coagulation factors of 40 healthy and 40 type 2 diabetics were determined experimentally. The data were then analyzed using SPSS and AMOS software. Multivariate regression analysis was done to draw path diagrams. RESULTS Our results show that FII, as the main cause for hypercoagulable state, is directly induced by FX and FVIII in normal individuals and by FX, FXI, FV and VWF cofactors in diabetic patients. CONCLUSION In general, our findings showed complicated relationship between coagulation factors and their effects either separately or combined.
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Affiliation(s)
- Mohammad Reza Dayer
- 1. Assistant Professor, Department of Biology, Faculty of Science, Shahid Chamran University, Ahvaz, Iran.
| | - Maysam Mard-Soltani
- 2. Medical Education Development Center, Dezful University of Medical Sciences, Dezful, Iran.
| | - Mohammad Saaid Dayer
- 3. Assistant Professor, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Sayed Mohammad Reza Alavi
- 4. Assistant Professor, Department of Statistics, Faculty of Mathematics and Computer Sciences, Shahid Chamran University, Ahvaz, Iran.
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Shang J, Chen Z, Wang M, Li Q, Feng W, Wu Y, Wu W, Graziano MP, Chintala M. Zucker Diabetic Fatty rats exhibit hypercoagulability and accelerated thrombus formation in the Arterio-Venous shunt model of thrombosis. Thromb Res 2014; 134:433-9. [PMID: 24796819 DOI: 10.1016/j.thromres.2014.04.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2014] [Revised: 04/06/2014] [Accepted: 04/08/2014] [Indexed: 11/18/2022]
Abstract
INTRODUCTION Diabetes is a significant risk factor for thrombosis. The present study aimed at assessing coagulability, platelet reactivity, and thrombogenicity of the diabetic female Zucker Diabetic Fatty (ZDF) rat model and its relevance in studying antithrombotic mechanisms. MATERIALS AND METHODS The basal coagulant state in ZDF rats was evaluated by clotting times, thromboelastography, and thrombin generation assay. A 14-day treatment with dapagliflozin in ZDF rats was pursued to investigate if glycemic control can improve coagulability. Thrombus formation in the Arterio-Venous (A-V) shunt model and the FeCl3-induced arterial thrombosis model was studied, with the antithrombotic effect of apixaban in the former model further investigated. RESULTS ZDF rats exhibited significantly shortened clotting times, enhanced thrombin generation, and decreased fibrinolysis at baseline. Effective glycemic control achieved with dapagliflozin did not improve any of these parameters. ZDF rats displayed accelerated thrombus formation and were amenable to apixaban treatment in the A-V shunt model albeit with less sensitivity than normal rats. ZDF rats exhibited less platelet aggregation in response to ADP, collagen and PAR-4, and attenuated thrombotic response in the FeCl3 model. CONCLUSIONS ZDF rats are at a chronic hypercoagulable and hypofibrinolytic state yet with compromised platelet reactivity. They display accelerated and attenuated thrombosis in the A-V shunt and FeCl3 model of thrombosis, respectively. Results shed new light on the pathophysiology of the ZDF rat model and illustrate its potential value in translational research on anticoagulant agents in diabetics. Caution needs to be exerted in utilizing this model in assessing antiplatelet mechanisms in diabetes-associated atherothrombosis.
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Affiliation(s)
- Jin Shang
- Department of Cardiometabolic Disease, Merck Research Laboratories, Kenilworth, New Jersey.
| | - Zhu Chen
- Department of Cardiometabolic Disease, Merck Research Laboratories, Kenilworth, New Jersey.
| | - Min Wang
- Department of Cardiometabolic Disease, Merck Research Laboratories, Kenilworth, New Jersey
| | - Qiu Li
- Department of Cardiometabolic Disease, Merck Research Laboratories, Kenilworth, New Jersey
| | - Wen Feng
- Department of Cardiometabolic Disease, Merck Research Laboratories, Kenilworth, New Jersey
| | - Yangsong Wu
- Department of Cardiometabolic Disease, Merck Research Laboratories, Kenilworth, New Jersey
| | - Weizhen Wu
- Department of Cardiometabolic Disease, Merck Research Laboratories, Kenilworth, New Jersey
| | - Michael P Graziano
- Department of Cardiometabolic Disease, Merck Research Laboratories, Kenilworth, New Jersey
| | - Madhu Chintala
- Department of Cardiometabolic Disease, Merck Research Laboratories, Kenilworth, New Jersey
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Habib SS. Plasma tissue factor pathway inhibitor levels in angiographically defined coronary artery disease among saudis. Oman Med J 2013; 28:191-4. [PMID: 23772285 DOI: 10.5001/omj.2013.52] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2013] [Accepted: 03/26/2013] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVES This study was aimed to determine plasma levels of total (TFPI-T) and free (TFPI-F) tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA) in a cohort of Saudi patients with chronic stable angiographically defined coronary artery disease (CAD) and to determine its correlation with its severity. METHODS This cross sectional study was conducted in the department of physiology and department of cardiology, College of Medicine, and King Khalid University Hospital and King Saud University, Riyadh. Sixty known cases of CAD who had undergone angiography (35 males and 25 females) were selected. A control group included 39 (20 males and 19 females) healthy subjects. Fasting venous blood samples were analyzed for total (TFPI-T) and free (TFPI-F) tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA). Gensini scores and vessel scores were determined for assessing CAD severity. RESULTS There were non-significant differences between age, body mass index (BMI) and Blood pressure between the controls and CAD subjects. A comparison of hemostatic markers between control and CAD patients showed significantly higher levels of Fibrinogen, PAI-1, TFPI-T and TFPI-F in CAD patients compared to control subjects. But there was no difference in plasma t-PA levels. TFPI-T had a significant positive correlation with severity of disease determined by Gensini Scores (r=0.344; p=0.006) and vessel scores (r=0.338; p=0.015). CONCLUSION Plasma levels of total tissue factor pathway inhibitor are significantly related with the presence and severity of CAD. Elevated levels of TFPI-T may be considered as useful diagnostic and prognostic markers in patients with CAD.
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Affiliation(s)
- Syed Shahid Habib
- Associate Professor, Department of Physiology (29), College of Medicine, PO Box 2925, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia
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