Christina Kollia

Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease

BACKGROUND Osteopontin (OPN) and osteoprotegerin (OPG) have recently emerged as key factors in both vascular remodeling and development of atherosclerosis. Arterial stiffness has an independent predictive value for cardiovascular events. We evaluate the relationship between OPG, OPN serum levels and vascular function in coronary artery disease (CAD) patients. METHODS The study population was consisted of 409 subjects (280 with CAD and 129 without CAD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. OPG and OPN levels were measured, as markers of vascular remodeling and calcification, by ELISA. Gensini score was used to evaluate the extent of CAD. RESULTS CAD patients, compared to those without CAD, had higher OPG (3.91 ± 1.87 pmol/l vs. 2.88 ± 1.32 pmol/l, p<0.001) and logOPN levels (1.81 ± 0.18 ng/ml vs. 1.71 ± 0.24 ng/ml, p<0.001) and impaired PWV (8.94 ± 2.21 m/s vs. 8.28 ± 1.91 m/s, p=0.006). Furthermore, PWV was associated with serum OPG levels (r=0.19, p<0.001) and with serum logOPN levels (r=0.10, p=0.049). Multivariate linear regression analysis revealed that increased OPG (p=0.013) and logOPN (p=0.006) levels are associated with 3-vessel CAD and Gensini score (p=0.04 for OPG and p=0.09 for OPN), independently of other known cardiovascular risk factors. CONCLUSION The present study revealed that serum OPG and OPN levels are positively associated with arterial stiffness, and with the extent of CAD. These preliminary results suggest that OPG and OPN levels are significantly correlated with vascular function contributing to the pathogenesis of atherosclerosis in CAD. Further studies are needed to explore the mechanisms of action of OPG and OPN in CAD.

Role of Endothelial Dysfunction and Arterial Stiffness in the Development of Diabetic Retinopathy

Diabetic retinopathy (DR) remains one of the most important diabetic microvascular complications and a leading cause of irreversible blindness, highlighting the importance of close monitoring. The atherosclerotic progression in patients with insulin resistance is precipitated by endothelial dysfunction and vascular impairment (1). Therefore, we examined the association of endothelial dysfunction and arterial stiffness with DR and how these measurements can be used for the early identification and monitoring of patients at high risk to develop DR. In this case-control study, we included 100 healthy control (CL) subjects and 200 consecutive subjects with type 2 diabetes recruited from the 1st Department of Ophthalmology of the University of Athens Medical School where they were referred to evaluate for DR. All participants underwent a complete ophthalmological examination by the same experienced ophthalmologist, which included fundoscopy after pupillary dilation, fluorescein angiography, and colorful fundus photographs. The diabetic patients, according to the Early Treatment Diabetic Retinopathy Study (ETDRS) classification, were categorized into three groups: 1 ) no DR (NDR) (108 …

MicroRNAs in Cardiovascular Therapeutics

Recent research reveals the crucial role microRNAs (miRNAs) in the pathogenesis and progression of many pathological conditions, including cardiovascular diseases. It is widely documented that miRNAs represent critical regulators of cardiovascular function and participate in almost all aspects of cardiovascular biology. In particular, they are involved in several pathophysiological pathways of various manifestations of cardiovascular disease, such as coronary artery disease, heart failure, stroke, diabetes mellitus, arterial hypertension and cardiac arrhythmias. In the present article we review the available literature regarding to the role of miRNAs in certain cardiovascular conditions. Moreover, we discuss the therapeutic potential of miRNAs for treating cardiovascular diseases and we attempt to highlight future directions.

MicroRNAs: Novel Diagnostic and Prognostic Biomarkers in Atherosclerosis

MicroRNAs (miRNAs) are an emerging class of highly conserved, non-coding small RNAs that regulate gene expression on the post-transcriptional level by inhibiting the translation of protein from mRNA or by promoting the degradation of mRNA. The involvement of miRNAs in the regulation of lipid metabolism, inflammatory response, cell cycle progression and proliferation, oxidative stress, platelet activation, endothelial function, angiogenesis and plaque formation and rapture indicates important roles in the initiation and progression of atherosclerosis. In the light of this evidence we will review the role of miRNAs in atherosclerosis.

Arterial Wall Elastic Properties and Endothelial Dysfunction in the Diabetic Foot Syndrome in Patients With Type 2 Diabetes

Diabetic foot (DF) syndrome is the most common lower-extremity complication of poorly controlled type 2 diabetes (T2D) (1). DF affects the quality of life of T2D patients and is associated with increased morbidity (2). T2D-related mechanisms induce endothelial dysfunction and adverse effects on vascular biology (3). We have recently shown that measurements of endothelial function and arterial stiffness are strongly associated with diabetic retinopathy (4), but their association with DF has not been explored yet. To examine this, we enrolled 284 consecutive T2D subjects visiting our outpatient diabetes clinic and 196 age- and sex-matched healthy control subjects without evidence of diabetes or cardiovascular or other disease. Subjects with known malignancy, hepatic impairment, or acute or chronic inflammatory disease were excluded from the study. Study protocol was approved by the institutional ethics committee. Endothelial function was assessed by the flow-mediated dilation (FMD) of the brachial artery and carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) were assessed by SphygmoCor (AtCor Medical) as …

The impact of T786C and G894T polymorphisms of eNOS on vascular endothelial growth factor serum levels in type 2 diabetes patients.

Endothelial dysfunction (ED) and chemokines such as vascular endothelial growth factor (VEGF) are of vital importance for the development of diabetic vascular complications [1–3]. VEGF is a secreted mitogen which plays a key role in the regulation of angiogenesis, vasculogenesis and vascular permeability to water and proteins [4]. Moreover, the action of VEGF is crucial for themaintenance of the proper endothelial and vascular function. The interaction between VEGF and its receptors is disrupted in diabetes, leading to pathological angiogenesis,which in turn contributes tomicrovascular diseases, such as diabetic retinopathy and diabetic nephropathy [5]. Nitric oxide (NO) is the most important regulator of vascular homeostasis and therefore, a common feature of ED is its diminished bioavailability in the vasculature [6,7]. In the setting of diabetes and insulin resistance, the activity of endothelial nitric oxide synthase (eNOS) is impaired, since insulin-mediated activation of eNOS via PI3kinase/Akt pathway is inhibited [8]. Moreover, diabetes mellitus (DM) enhances the production of reactive oxygen species (ROS), thus resulting in less NO generation and consequent vascular dysfunction [9,10].

Associations between Adiponectin Gene Variability, Pro-inflammatory and Angiogenetic Markers: Implications for Microvascular Disease Development in Type 2 Diabetes Mellitus?

BACKGROUND Adiponectin gene (ADIPOQ) variability may affect the risk for type 2 diabetes mellitus (T2DM) but it remains unclear whether it is involved in microvascular complications. OBJECTIVE To explore the impact of ADIPOQ variability on markers of inflammation and angiogenesis in T2DM. METHODS Overall, 220 consecutive T2DM patients from our outpatient diabetic clinic were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene. Serum levels of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay and high sensitivity Creactive protein (hsCRP) by immunonephelometry. RESULTS Homozygosity for the G allele on rs2241766 was associated with significantly lower serum VEGF and ICAM-1 levels compared with other genotype groups, but had no effect on IL-6. Genetic variability on rs1501299 was not associated with either VEGF or ICAM-1 levels, but T homozygotes for rs1501299 had significantly lower IL-6 concentrations compared with G carriers. Furthermore, the presence of the G allele on rs2241766 was associated with significantly lower HbA1c, whereas no associations were observed for both body mass index and hsCRP with either rs2241766 or rs1501299. CONCLUSION Genetic variability on adiponectin gene was associated with serum levels of inflammatory and angiogenetic markers. Further research is required to elucidate the role of adiponectin in the development and/or progression of microvascular disease in T2DM patients.

THE IMPACT OF ENDOTHELIAL DYSFUNCTION IN THE DEVELOPMENT OF DIABETIC RETINOPATHY: ROLE OF INFLAMMATION

Diabetic Retinopathy (DR) is a leading cause of blindness. Measurement of endothelial function and arterial stiffness are associated with adverse cardiovascular outcomes. We investigated the possible association of DR with endothelial function, arterial stiffness and inflammation. We enrolled 100

IMPAIRED ENDOTHELIAL FUNCTION AND INCREASED ARTERIAL STIFFNESS IN PATIENTS WITH DIABETIC RETINOPATHY

Diabetes Mellitus is associated with endothelial dysfunction and arterial stiffness. Diabetic Retinopathy (DR) is a complication of diabetes mellitus and remains a leading cause of irreversible blindness. We investigated the possible association of DR with endothelial function, arterial stiffness