Browsing by Author "Kaur, Savneet"
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Item Association of Monocyte Chemoattractant Protein-1-2518 Polymorphism With Metabolic Syndrome in a South Indian Cohort(METABOLIC SYNDROME AND RELATED DISORDERS, 2009)Background: Previous reports have indicated an association of monocyte chemoattractant protein-1 (MCP-1) with risk factors for atherosclerosis and coronary artery disease (CAD). Because some of these risk factors form components of metabolic syndrome, in the present study, we investigated the association of an important promoter region polymorphism of MCP-1, A-2518G, and its serum levels with metabolic syndrome in a South Indian cohort.Methods: The study comprised of 126 healthy subjects aged 30-59 years from South India. Subjects were classified on the basis of presence or absence of metabolic syndrome and metabolic syndrome components as per the International Diabetes Federation definition. MCP-1 genotyping was done by polymerase chain reaction restriction fragment-length polymorphism, and serum levels were estimated by enzyme-linked immunosorbent assay.Results: The MCP-1 -2518G allele frequency in the study population was 32.9% and the mean MCP-1 serum levels were 523 +/- 272.3 pg/mL. Subjects with metabolic syndrome showed an increased presence of the MCP-1-2518G allele in comparison to those without metabolic syndrome (odds ratio [OR] = 5.03, P = 0.02). The association was related to a higher proportion of this allele in subjects with increased waist circumference (OR = 3.78, P = 0.05).Conclusions: The MCP-1 -2518G allele may be contributing to atherosclerosis and CAD by conferring an increased risk to metabolic syndrome and/or obesity.Item Genetic engineering with endothelial nitric oxide synthase improves functional properties of endothelial progenitor cells from patients with coronary artery disease: an in vitro study(BASIC RESEARCH IN CARDIOLOGY, 2009)Recent studies have reported a marked impairment in the number and functions of endothelial progenitor cells (EPCs) in patients with coronary artery disease (CAD). In view of an important role of eNOS in angiogenesis, in the present study, we evaluated the effects of eNOS gene transfer in ex vivo expanded EPCs isolated from patients with CAD. The expanded EPCs were transfected with mammalian expression vector pcDNA3.1-eNOS containing the full-length human eNOS gene using lipofectamine. About 35-40% of the eNOS-EPCs had higher expression of eNOS as compared to untransfected EPCs. EPCs transfected with pcDNA3.0-EGFP, the plasmid vector expressing green fluorescent protein (GFP) were used as control. The untransfected, GFP-transfected and eNOS-transfected EPCs were compared in terms of important functional attributes of angiogenesis such as proliferation, migration, differentiation and adhesion/integration into tube-like structures in vitro. Functional studies revealed that in the presence of defined growth conditions, compared to the untransfected and GFP-transfected cells, eNOS-EPCs from patients with CAD have a significant increase in [(3)H] thymidine-labeled DNA (P < 0.01), migration (14.6 +/- A 1.8 and 16.5 +/- A 1.9 vs. 23.5 +/- A 3.4 cells/field, P < 0.01), ability to differentiate into endothelial-like spindle-shaped cells (46 +/- A 4.5 and 56.5 +/- A 2.1 vs. 93.2 +/- A 6.6 cells/field, P < 0.001) and also incorporation into tube-like structures on the matrigel (GFP-EPCs: 21.25 +/- A 2.9 vs. GFP-eNOS-EPCs: 34.5 +/- A 5.5 cells/field, P < 0.05). We conclude that eNOS gene transfection is a valuable approach to augment angiogenic properties of ex vivo expanded EPCs and eNOS-modified EPCs may offer significant advantages than EPCs alone in terms of their clinical use in patients with myocardial ischemia.Item The potential of circulating endothelial progenitor cells to form colonies is inversely proportional to total vascular risk score in patients with coronary artery disease.(Indian heart journal, 2007)OBJECTIVE: The present study correlated the functional ability of culture-enriched EPCs to form colonies (EPC-CFUs), with risk factors and severity of CAD.METHODS: Blood mononuclear cells from healthy controls (n = 16) and patients with CAD (n =35) were cultured for seven days for the formation of EPC-CFUs. After the characterization of EPCs, the number of EPC-clusters were compared in the study groups and correlated with the presence or absence of individual CAD risk factors, total vascular risk score (TVRS) and the severity of CAD in patients with CAD by Student's 't' test and regression analysis.RESULTS: As compared to the patients, the controls showed significantly greater formation of EPC-CFUs. Patients with hypertension and smoking had significant reduction in the number of EPC-CFUs as compared to patients without these risk factors (p < 0.05). A negative correlation between TVRS and number of EPC-CFUs (r = -0.74, p < 0.05) and also between number of stenosing coronary arteries and EPC-CFUs (r = -0.42, p = 0.05) were observed. On multivariate analysis, however, only TVRS appeared to be a significant predictor of reduced formation of EPC-CFUs.CONCLUSION: The present study suggests that more is the number of CAD risk factors, lesser is the formation of EPC-clusters in culture.