ABSTRACT
Vascular calcification is an important stage in atherosclerosis. During this stage, vascular smooth muscle cells [VSMC] synthesize many osteogenic factors such as osteonectin [encoded by SPARC]. Oxidative stress plays a critical role in atherosclerosis progression, and its accumulation in the vascular wall stimulates the development of atherosclerosis and vascular calcification. The osteonectin overexpression has been observed in the arterial wall during the course of atherosclerosis. However, the regulatory mechanism of oxidized low density lipoprotein [oxLDL]-mediated vascular calcification remains to be clarified. The aim of this study was to investigate the effect of oxLDL on the osteonectin gene expression through the Runx2 transcription factor. In this experimental study, VSMC were cultured in F-12K media and then treated with oxLDL. The expression of Runx2 and osteonectin genes was determined by real-time PCR method. Protein levels were investigated by the western blotting technique. The Runx2 gene was knocked down using siRNA in order to determine whether Runx2 regulates the osteonectin expression in VSMC induced by oxLDL. Then transfected cells were treated with oxLDL, and the expression levels of Runx2 and osteonectin were determined again. oxLDL was found to increase Runx2 and osteonectin gene expression [4.8 +/- 0.47- and 9.2 +/- 1.96-fold, respectively] after 48 h. Western blotting analysis confirmed the induced levels of Runx2 and osteonectin proteins. However, oxLDL-induced osteonectin expression was not observed to be blocked by Runx2 knockdown. The up-regulation of osteonectin by oxLDL is independent of Runx2, and it may be mediated by other transcription factors
ABSTRACT
Cholesteryl ester transfer protein [CETP] plays a main role in high-density lipoprotein metabolism. CETP gene possesses several single nucleotide polymorphisms which have been associated with plasma high-density lipoprotein cholesterol [HDL-C] concentrations. The aim of this study was to determine the association of CETP -629C/A and I405V polymorphisms with coronary artery disease [CAD] in Iranian population. The presence of two CETP gene polymorphisms -629C/A and I405V were studied in 187 unrelated CAD cases and 136 controls. All the samples were clinically examined and lipid profile was estimated. Genotyping was performed using polymerase chain reaction/restriction fragment length polymorphism method. The frequency of-629C/A and I405V allelic variants were found to be 0.732 and 0.366 in cases and 0.658 and 0.348 in controls, respectively. The frequency of A allele of -629C/A polymorphism in cases was significantly higher than that of controls. HDL-C in AA genotype was higher than CA and CC genotypes in controls. No significant effect of II, IV and VV genotypes was found in lipid profiles. No significant association was found between CETP I405V polymorphism and increased risk of CAD in Azeri population studied. AA genotype of -629C/A increased HDL but the risk of CAD in this genotype might be higher than CC genotype