• Atherosclerosis
• Cardiovascular disease
• Drug delivery
• Micro/nanomotors
• Nanomedicine

• Humans
• Atherosclerosis/drug therapy
• Atherosclerosis/diagnosis
• Plaque, Atherosclerotic/diagnostic imaging
• Plaque, Atherosclerotic/drug therapy
• Plaque, Atherosclerotic/diagnosis
• Animals
• Drug Delivery Systems

• atherosclerosis
• carotid stenosis
• osteoprotegerin
• stroke

• BNW-1-029/N/3/K. Medical University of Silesia in Katowice

• atherosclerosis
• calcification
• extracellular matrix proteins
• osteopontin
• osteoprotegerin

• atherosclerosis
• coronary artery disease
• osteopontin
• peripheral artery disease
• vascular calcification

• PCSK-9 inhibitors
• atherosclerotic plaque
• carotid MRI
• matrix metalloproteinases
• osteopontin
• osteoprotegerin

• Humans
• Plaque, Atherosclerotic/diagnostic imaging
• Plaque, Atherosclerotic/drug therapy
• Proprotein Convertase 9
• Atherosclerosis
• Ultrasonography

• PCN-1-185/N/9/O 2019 Medical University of Silesia

• biomarkers
• ischemic stroke
• osteoprotegerin
• prognosis
• risk factors

Vascular dementia (VaD) and carotid atherosclerotic plaques are common in the elderly population, conferring a heavy burden on families and society. Accumulating evidence indicates carotid atherosclerotic plaques to be a risk factor for VaD. However, the underlying mechanisms for this association are mainly unknown.

We analyzed temporal cortex gene expression data of the GSE122063 dataset and gene expression data of the GSE163154 dataset to identify commonly differentially expressed genes (DEGs). Then we performed functional enrichment analysis, immune cell infiltration and evaluation, correlation analysis between differentially expressed immune-related genes (DEIRGs) and immune cells, receiver operating characteristic (ROC) analysis, and drug-gene analysis.

We identified 41 overlapped DEGs between the VaD and carotid atherosclerosis plaque datasets. Functional enrichment analyses revealed that these overlapped DEGs were mainly enriched in inflammatory and immune-related processes. Immunocyte infiltration and evaluation results showed that M0 macrophages, M2 macrophages, and T cells gamma delta had a dominant abundance in carotid atherosclerosis plaque samples, and M0 macrophages showed a significantly different infiltration percentage between the early and advanced stage plaques group. Resting CD4 memory T cells, M2 macrophages, and naive B cells were the top three highest infiltrating fractions in VaD. Furthermore, B cells and NK cells showed a different infiltration percentage between VaD and matched controls. We identified 12 DEIRGs, and the result of correlation analysis revealed that these DEIRGs were closely related to differentially expressed immune cells. We identified five key DEIRGs based on ROC analysis. The drug-gene interaction analysis showed that four drugs (avacopan, CCX354, BMS-817399, and ASK-8007) could be potential drugs for VaD and carotid atherosclerotic plaques treatment.

Collectively, these findings indicated that inflammatory and immune-related processes be a crucial common pathophysiological mechanism shared by VaD and carotid plaques. This study might provide new insights into common molecular mechanisms between VaD and carotid plaques and potential targets for the treatment.

Vulnerable plaques have been a hot topic in the field of stroke and carotid atherosclerosis. Currently, risk stratification and intervention of carotid plaques are guided by the degree of luminal stenosis. Recently, it has been recognized that the vulnerability of plaques may contribute to the risk of stroke. Some classical interventions, such as carotid endarterectomy, significantly reduce the risk of stroke in symptomatic patients with severe carotid stenosis, while for asymptomatic patients, clinically silent plaques with rupture tendency may expose them to the risk of cerebrovascular events. Early identification of vulnerable plaques contributes to lowering the risk of cerebrovascular events. Previously, the identification of vulnerable plaques was commonly based on imaging technologies at the macroscopic level. Recently, some microscopic molecules pertaining to vulnerable plaques have emerged, and could be potential biomarkers or therapeutic targets. This review aimed to update the previous summarization of vulnerable plaques and identify vulnerable plaques at the microscopic and macroscopic levels.

• Atherosclerosis
• Cardiovascular disease
• Immune dysregulation
• Pathogenesis
• Risk stratification
• Systemic lupus erythematosus

Osteoporosis is the most common bone tissue disease and it is characterized by a reduced bone mineral density (BMD). The main physiopathological mechanisms converge on the uncoupling between bone formation and resorption, thus leading to an enhanced risk of fractures. Several papers have documented the inverse relationships linking high inflammatory cytokines, anti-citrullinated protein antibodies, rheumatoid factor, and BMD in rheumatoid arthritis (RA). Rituximab (RTX) is a chimeric monoclonal antibody directed against the CD20 receptor of B cells. Since the Food and Drug Administration approved it for RA in 2006, there have been many clinical experiences regarding its use. Nevertheless, few studies evaluate the effect of rituximab on BMD. RA is a disease characterized by immune dysfunction with high levels of inflammatory cytokines, autoantibodies, and it is reasonable that a B cell depleting therapy could restore a physiological cytokine balance, thus exerting an osteoprotective effect on the bone tissue. The purpose of this paper is to highlight any difference in BMD and to assess differences in body composition over a retrospective 18-month follow-up period after RTX treatment with a B cell depleting therapy.

We analyzed by dual energy X-ray absorptiometry BMD expressed as g/cm² and body composition modifications over 18 months with RTX treatment of 20 postmenopausal RA patients.

After eighteen months of therapy with RTX, a statistically significant increase in vertebral (L1–L4) BMD and the stability of femoral BMD were documented.

Rituximab is associated with an improvement of vertebral and preservation of femoral BMD, suggesting a bone-sparing effect due to B cell depletion. Furthermore, patients displayed a redistribution of fat masses toward the hip region.

• bone
• osteoporosis
• rheumatoid arthritis
• rituximab

• Biomarkers
• Hemodialysis access
• Osteopontin
• Surgical arteriovenous shunt

• Osteoporosis
• bone
• calcification paradox
• cardiovascular disease (CVD)
• osteoprotegerin
• statins

Cerebrovascular disease (CeVD) and neurodegenerative dementia such as Alzheimer’s disease (AD) are frequently associated comorbidities in the elderly, sharing common risk factors and pathophysiological mechanisms including neuroinflammation. Osteopontin (OPN) is an inflammatory marker found upregulated in vascular diseases as well as in AD. However, its involvement in vascular dementia (VaD) and pre-dementia stages, namely cognitive impairment no dementia (CIND), both of which fall under the spectrum of vascular cognitive impairment (VCI), has yet to be examined. Its correlations with inflammatory cytokines in cognitive impairment also await investigation. 80 subjects with no cognitive impairment (NCI), 160 with CIND and 144 with dementia were included in a cross-sectional study on a Singapore-based memory clinic cohort. All subjects underwent comprehensive clinical, neuropsychological and brain neuroimaging assessments, together with clinical diagnoses based on established criteria. Blood samples were collected and OPN as well as inflammatory cytokines interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF) were measured using immunoassays. Multivariate regression analyses showed significant associations between increased OPN and VCI groups, namely CIND with CeVD, AD with CeVD and VaD. Interestingly, higher OPN was also significantly associated with AD even in the absence of CeVD. We further showed that increased OPN significantly associated with neuroimaging markers of CeVD and neurodegeneration, including cortical infarcts, lacunes, white matter hyperintensities and brain atrophy. OPN also correlated with elevated levels of IL-6, IL-8 and TNF. Our findings suggest that OPN may play a role in both VCI and neurodegenerative dementias. Further longitudinal analyses are needed to assess the prognostic utility of OPN in disease prediction and monitoring.

• atherosclerotic plaque
• calcification
• calcification markers
• coronary atherosclerosis

• Abdominal aortic aneurysm
• Fenofibrate
• Macrophage
• Osteopontin
• Randomised controlled trial

• Aged
• Aorta, Abdominal/drug effects
• Aorta, Abdominal/metabolism
• Aorta, Abdominal/pathology
• Aorta, Abdominal/surgery
• Aortic Aneurysm, Abdominal/blood
• Aortic Aneurysm, Abdominal/pathology
• Aortic Aneurysm, Abdominal/therapy
• Biomarkers/blood
• Disease Progression
• Double-Blind Method
• Drug Administration Schedule
• Female
• Fenofibrate/administration & dosage
• Fenofibrate/adverse effects
• Humans
• Macrophages/pathology
• Male
• Middle Aged
• Osteopontin/blood
• Queensland
• Time Factors
• Treatment Outcome
• Triglycerides/blood
• Vascular Remodeling/drug effects
• Vascular Surgical Procedures/adverse effects

• atherosclerosis
• osteopontin
• osteoprotegerin
• ultrasonography
• immunohistochemistry

• Biomarkers
• Female
• Humans
• Male
• Osteopontin
• Osteoprotegerin
• Plaque, Atherosclerotic
• Vascular Calcification

• bone mineral density
• bone–vascular axis
• end-stage renal disease
• mortality
• osteoporosis
• vascular calcification

• Baxter Healthcare to Karolinska Institutet
• Karolinska Institutet Diabetes Theme Center
• European Union’s Horizon 2020
• Heart and Lung Foundation

• In-stent restenosis
• Neointimal hyperplasia
• OPG
• YAP
• αVβ3

Instability of atherosclerotic plaques is associated with the occurrence of stroke. Microembolic signals (MESs) are an indicator of unstable plaque. A relationship between plasma osteoprotegerin (OPG) and ischemic stroke has already been identified. The aim of this study was to investigate whether plasma OPG levels have a relationship with MESs and to evaluate the feasibility of OPG as a biomarker of stroke severity and occurrence of MESs.

Our study consisted of 127 patients with large artery atherosclerosis stroke and 56 controls. Patients were classified into subgroups based on stroke severity and the occurrence of MESs. MES-monitoring was performed for 60 min using transcranial Doppler within 72 h of stroke onset. Stroke severity at admission was assessed by the National Institutes of Health Stroke Scale.

Plasma OPG levels were significantly associated with stroke, MESs, and stroke severity at admission (adjusted OR [95% CI]: 1.002 [1.001–1.003] p < 0.001; 1.002 [1.001–1.003] p = 0.001; 1.001 [1.000–1.002] p = 0.028). When plasma OPG levels were used to determine the stroke severity, the area under the receiver-operating characteristic curve (AUC) was 0.734 (95% CI: 0.625-0.843) based on a cutoff value of 1998.44 pg/ml; the sensitivity and specificity of this test were 80.6% and 65.6%, respectively. Furthermore, when the levels of OPG were used to distinguish the presence of MESs, the AUC was 0.766 (95% CI: 0.672-0.860); the cutoff value was 2107.91 pg/ml. The sensitivity of this cutoff value was 68.8% and the specificity was 73.7%.

Plasma OPG levels correlate with stroke severity and the occurrence of MESs.

• C-reactive protein
• carotid intima-media thickness
• osteopontin and atherosclerosis
• systemic lupus erythematosus

Cardiac β₂-adrenergic receptors (ARs) are known to inhibit collagen production and fibrosis in cardiac fibroblasts and myocytes. The β₂AR is a Gs protein-coupled receptor (GPCR) and, upon its activation, stimulates the generation of cyclic 3′,5′-adenosine monophosphate (cAMP). cAMP has two effectors: protein kinase A (PKA) and the exchange protein directly activated by cAMP (Epac). Epac1 has been shown to inhibit cardiac fibroblast activation and fibrosis. Osteopontin (OPN) is a ubiquitous pro-inflammatory cytokine, which also mediates fibrosis in several tissues, including the heart. OPN underlies several cardiovascular pathologies, including atherosclerosis and cardiac adverse remodeling. We found that the cardiotoxic hormone aldosterone transcriptionally upregulates OPN in H9c2 rat cardiac myoblasts—an effect prevented by endogenous β₂AR activation. Additionally, CRISPR-mediated OPN deletion enhanced cAMP generation in response to both β₁AR and β₂AR activation in H9c2 cardiomyocytes, leading to the upregulation of Epac1 protein levels. These effects rendered β₂AR stimulation capable of completely abrogating transforming growth factor (TGF)-β-dependent fibrosis in OPN-lacking H9c2 cardiomyocytes. Finally, OPN interacted constitutively with G_αs subunits in H9c2 cardiac cells. Thus, we uncovered a direct inhibitory role of OPN in cardiac β₂AR anti-fibrotic signaling via cAMP/Epac1. OPN blockade could be of value in the treatment and/or prevention of cardiac fibrosis.

• CRISPR
• Epac1
• cAMP
• cardiac myocytes
• fibrosis
• osteopontin
• signal transduction
• β2-adrenergic receptor

• Animals
• Blotting, Western
• Cell Line
• Clustered Regularly Interspaced Short Palindromic Repeats/genetics
• Clustered Regularly Interspaced Short Palindromic Repeats/physiology
• Cyclic AMP/genetics
• Cyclic AMP/metabolism
• Fibrosis/genetics
• Fibrosis/metabolism
• Guanine Nucleotide Exchange Factors/genetics
• Guanine Nucleotide Exchange Factors/metabolism
• Immunoprecipitation
• Myocytes, Cardiac/metabolism
• Osteopontin/genetics
• Osteopontin/metabolism
• Rats
• Real-Time Polymerase Chain Reaction
• Receptors, Adrenergic, beta/genetics
• Receptors, Adrenergic, beta/metabolism
• Signal Transduction/genetics
• Signal Transduction/physiology

• R01 HL140468 NHLBI NIH HHS

Atherosclerosis is an inflammatory process resulting in local plaque deposition in the vessel wall of arteries with symptoms to various areas of vascular tree. Identification of patients with progressive advanced atherosclerotic disease is mainly based on the known characteristics of the vulnerable or recently ruptured plaque. Molecular and cellular features associated with the vulnerable plaque are considered potential diagnostic markers for plaque rupture and thrombosis. Here, protein expression levels of the metalloproteases MMP-1, MMP-9, osteopontin (OPN), and cytokines TNFα and IL-6 in tissue extracts of carotid plaques in patients after endarterectomy were estimated by Western immunoblotting, after SDS-PAGE analysis and evaluated based on the ultrasonographic plaque morphology. The gender and age effect was also examined. MMP-1, MMP-9, and IL-6 were expressed in higher levels compared to OPN and TNFa as well as in symptomatic (with type II and III carotid plaque classification) than asymptomatic (type IV) patients with differences considered statistically significant (P values <0.05). A significant positive correlation between MMP-1 and IL-6 (with Pearson correlation coefficient 0.748) is also notable. The data give further insight into the possible role of specific biomarker and enhance the need for further studies in order to clarify the proper one(s) for detection of the vulnerable plaque and help identify patients at risk for cardiovascular events.

• OPG/RANKL
• childhood diabetes
• endothelial dysfunction
• microalbuminuria
• obesity

• cardiovascular disease
• high‐risk population
• meta‐analysis
• osteoprotegerin
• prospective cohorts

• Acute Coronary Syndrome/epidemiology
• Angina Pectoris/blood
• Angina Pectoris/epidemiology
• Biomarkers/blood
• Cardiovascular Diseases/blood
• Cardiovascular Diseases/mortality
• Comorbidity
• Diabetes Mellitus/epidemiology
• Heart Diseases/epidemiology
• Humans
• Kidney Diseases/epidemiology
• Myocardial Infarction/blood
• Myocardial Infarction/epidemiology
• Myocardial Revascularization/statistics & numerical data
• Osteoprotegerin/blood
• Risk
• Stroke/blood
• Stroke/epidemiology

• atherosclerosis
• calcification factors
• carotid plaque
• matrix metalloproteinases
• vulnerability

Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease (NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome (MetS), like insulin resistance (IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, MetS, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin (OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesity-related comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of MetS as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.

• Nonalcoholic fatty liver disease
• Insulin resistance
• Metabolic syndrome
• Osteoprotegerin
• Receptor activator of nuclear factor kappa B
• Receptor activator of nuclear factor kappa B ligand

• Animals
• Comorbidity
• Humans
• Liver/pathology
• Non-alcoholic Fatty Liver Disease/blood
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/metabolism
• Non-alcoholic Fatty Liver Disease/pathology
• Obesity/blood
• Obesity/epidemiology
• Obesity/metabolism
• Obesity/pathology
• Osteoprotegerin/blood
• Osteoprotegerin/metabolism
• Prevalence
• RANK Ligand/metabolism
• Receptor Activator of Nuclear Factor-kappa B/metabolism
• Signal Transduction

• arterial stiffness
• atherosclerosis
• coronary artery disease
• osteoprotegerin
• prognosis
• vascular calcification

Osteoprotegerin (OPG) is a soluble decoy receptor for tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). It belongs to the tumor necrosis factor receptor superfamily (TNFRSF). OPG was initially discovered to contribute to homeostasis of bone turnover due to its capability of binding to receptor activator of nuclear factor-kappaB (NF-kB). However, apart from bone turnover, OPG plays important and diverse role(s) in many biological functions. Besides having anti-osteoclastic activity, OPG is thought to exert a protective anti-apoptotic action in OPG-expressing tumors by overcoming the physiologic mechanism of tumor surveillance exerted by TRAIL. Along with inhibiting TRAIL induced apoptosis, it can induce proliferation by binding to various cell surface receptors and thus turning on the canonical cell survival and proliferative pathways. OPG also induces angiogenesis, one of the hallmarks of cancer, thus facilitating tumor growth. Recently, the understanding of OPG and its different roles has been augmented substantially. This review is aimed at providing a very informative overview as to how OPG affects cancer progression especially breast cancer.

• COX-2
• FASN
• NF-kB
• PGE2
• osteoprotegerin

• Osteoprotegerin
• peripheral arterial disease
• toe-brachial index
• type 2 diabetes mellitus

HIV infection leads to severe B cell dysfunction, which manifests as impaired humoral immune response to infection and vaccinations and is not completely reversed by otherwise effective antiretroviral therapy (ART). Despite its inability to correct HIV-induced B cell dysfunction, ART has led to significantly increased lifespans in people living with HIV/AIDS. This has in turn led to escalating prevalence of non-AIDS complications in aging HIV-infected individuals, including malignancies, cardiovascular disease, bone disease, and other end-organ damage. These complications, typically associated with aging, are a significant cause of morbidity and mortality and occur significantly earlier in HIV-infected individuals. Understanding the pathophysiology of these comorbidities and delineating clinical management strategies and potential cures is gaining in importance. Bone loss and osteoporosis, which lead to increase in fragility fracture prevalence, have in recent years emerged as important non-AIDS comorbidities in patients with chronic HIV infection. Interestingly, ART exacerbates bone loss, particularly within the first couple of years following initiation. The mechanisms underlying HIV-induced bone loss are multifactorial and complicated by the fact that HIV infection is linked to multiple risk factors for osteoporosis and fracture, but a very interesting role for B cells in HIV-induced bone loss has recently emerged. Although best known for their important antibody-producing capabilities, B cells also produce two cytokines critical for bone metabolism: the key osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL) and its physiological inhibitor osteoprotegerin (OPG). Dysregulated B cell production of OPG and RANKL was shown to be a major contributor to increased bone loss and fracture risk in animal models and HIV-infected humans. This review will summarize our current knowledge of the role of the OPG/RANK–RANKL pathway in B cells in health and disease, and the contribution of B cells to HIV-induced bone loss. Data from mouse studies indicate that RANKL and OPG may also play a role in B cell function and the implications of these findings for human B cell biology, as well as therapeutic strategies targeting the OPG/RANK–RANKL pathway, will be discussed.

• B cells
• HIV
• bone loss
• comorbidities
• cytokines
• end-organ damage

• biomarkers
• hydroxymethylglutaryl-CoA reductase inhibitors
• proteomics
• risk factors
• stroke

Recent experimental and epidemiological studies have suggested that osteoprotegerin, a key regulator in bone metabolism, may be involved in vascular calcification and atherosclerosis. Our aim was to reliably quantify the associations of osteoprotegerin concentration and incidence of first-ever cardiovascular disease outcomes in the general population.

Using the electronic databases MEDLINE, EMBASE and Web of Science (January 1975 and April 2017, no language restrictions), nine relevant studies were identified involving a total of 26,442 participants recruited from the general population. Over a mean follow-up of 8.5 years, 2,160 cardiovascular disease, 2,123 coronary heart disease, and 1,102 stroke outcomes were recorded. Study-specific risk ratios were combined with random-effects meta-analysis.

When comparing individuals in the top with those in the bottom third of osteoprotegerin concentration, the combined risk ratio was 1.83 (95% confidence interval: 1.46, 2.30; P<0.001; I² = 76.8%) for cardiovascular disease, 1.72 for coronary heart disease (1.26, 2.37; P = 0.001; I² = 83.5%), and 1.58 for stroke (1.18, 2.12; P = 0.002; I² = 65.2%). Associations appeared stronger at younger age (P = 0.018 for cardiovascular disease), in studies that did not employ statistical adjustment (P = 0.023 for cardiovascular disease and 0.018 for coronary heart disease), and potentially in studies that measured osteoprotegerin in plasma rather than in serum (P = 0.005 for cardiovascular disease and 0.018 for coronary heart disease). Magnitudes of associations did not differ according to the proportion of males, geographical region, or osteoprotegerin assay manufacturer. There was no evidence for publication bias for any of the outcomes assessed (all P>0.05).

Elevated osteoprotegerin concentration is associated with an increased risk of incident cardiovascular disease in the general population. The mechanisms underlying this observation deserve further investigation.

• Cardiovascular Diseases/blood
• Cardiovascular Diseases/epidemiology
• Humans
• Incidence
• Osteoprotegerin/blood
• Risk Factors

• Austrian Research Promotion Agency FFG

• Atherosclerosis
• Cardiovascular risk marker
• Epidemiology
• Protein
• Renal disease

Atherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention.

We searched the PubMed database for recently published research articles up to June 2016, with the key words of “risk factors”, “outcomes”, “blood components”, “molecular mechanisms”, “cellular mechanisms”, and “human carotid atherosclerotic plaques”.

The articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected.

This review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque.

Carotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis.

Angiogenesis plays a critical role in the progression and vulnerability of atherosclerotic plaques; however, the orchestration of angiogenesis in atherosclerotic plaque formation remains unclear. The results of microarray analysis, real-time PCR and immunohistochemical analyses showed that Hairy/enhancer of split homologue-1 (Hes-1) expression was significantly decreased, while that of osteopontin (OPN) was increased, in atherosclerotic plaques. Meanwhile, immunofluorescence results demonstrated that both Hes-1 and OPN were expressed in endothelial cells (ECs) of neovessels in atherosclerotic plaques. The results of an in vitro study showed that Hes-1 was downregulated, while OPN was upregulated, in a time- and dose-dependent manner in human umbilical vein endothelial cells (HUVECs) by VEGF treatment. In addition, Hes-1 knockdown was found to have transcriptional promotion effect on OPN expression in HUVECs and enhance OPN-induced angiogenesis in response to VEGF. On the contrary, Hes-1 overexpression inhibited OPN expression in HUVECs and reduced angiogenesis in vitro and in vivo. The results of this study suggest that decreased Hes-1 expression in atherosclerotic plaques exaggerate VEGF-induced angiogenesis by upregulating OPN. Therefore, restoring Hes-1 expression and inhibiting OPN expression may be a promising strategy to prevent vulnerable plaque formation in patients with atherosclerosis.

Since 1991 many studies evaluated the link between cardiovascular diseases and osteoporosis, two age-related conditions, but the main common pathologic pathway has not been determined yet. The histological similarity between arterial calcified plaque and bone matrix and involvement of similar cells and mediators provide a special field of research. Therefore in the present study, we aimed to evaluate the relationship between coronary artery calcium score (CACS) as a surrogate marker of atherosclerosis and bone mediators and parameters in postmenopausal women.

Eleven postmenopausal women who had CACS higher than 80 were enrolled into the study and underwent bone densitometry. In addition, their serum and urine samples were taken for measuring osteoprotegerin, osteocalcin, and β cross laps. Patients' 10-year probability of fracture was calculated by the World Health Organization fracture-risk assessment tool (FRAX).

The regression analysis of our results showed the association between CACS and OC (std β=0.66, 95% confidence interval [CI] 5.47-72.27, P=0.027), femoral bone density (std β=−0.6, 95% CI -6864.34-14.27, P=0.05) and T-score (std β=−0.6, 95% CI −773.08-1.28, P=0.05) which remained significant after adjustment for age, weight, years since menopause and body mass index. No association was found between CACS and osteoprotegerin, spinal bone density and FRAX score.

In conclusion, this pilot study with small sample size showed the potential association between CACS and osteocalcin, femoral bone density and T-score. However, the relationship between CACS and osteoprotegerin, receptor activator of nuclear factor-kappa B ligand, FRAX score and other bone parameters remain to be clarified in larger sample size studies.

• Bone density
• Calcium
• Coronary artery disease
• Osteocalcin
• Osteoprotegerin

Abdominal aortic aneurysm (AAA) is a slowly progressive destructive process of the main abdominal artery. Experimental studies indicate that fibrates exert beneficial effects on AAAs by mechanisms involving both serum lipid modification and favourable changes to the AAA wall.

Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME) is a multicentre, randomised, double-blind, placebo-controlled clinical trial to assess the effect of orally administered therapy with fenofibrate on key pathological markers of AAA in patients undergoing open AAA repair. A total of 42 participants scheduled for an elective open AAA repair will be randomly assigned to either 145 mg of fenofibrate per day or identical placebo for a minimum period of 2 weeks prior to surgery. Primary outcome measures will be macrophage number and osteopontin (OPN) concentration within the AAA wall as well as serum concentrations of OPN. Secondary outcome measures will include levels of matrix metalloproteinases and proinflammatory cytokines within the AAA wall, periaortic fat and intramural thrombus and circulating concentrations of AAA biomarkers.

At present, there is no recognised medical therapy to limit AAA progression. The FAME trial aims to assess the ability of fenofibrate to alter tissue markers of AAA pathology.

Australian New Zealand Clinical Trials Registry, ACTRN12612001226897. Registered on 20 November 2012.

The online version of this article (doi:10.1186/s13063-016-1752-z) contains supplementary material, which is available to authorized users.

• Abdominal aortic aneurysm
• Clinical trial
• Fenofibrate
• Macrophage
• Osteopontin