MMP-1 polymorphic expression in aortic endothelial cells: possible role in lesion development in smokers and nonsmokers.

Abstract

Matrix metalloproteinase-1 (MMP-1) is involved in the degradation of extra-cellular matrix components and is thought to play a key role in atherogenesis. The objective of the present study was to determine: (1) whether MMP-1 differential gene expression observed in primary cultures of human aortic endothelial cells (HAEC) exposed to cigarette smoke condensate (CSC) was associated with a single nucleotide polymorphism (SNP) in its promoter region and (2) if the SNP altered atherosclerotic lesion development in smokers and nonsmokers. Genotype analysis of six HAEC lines revealed that those homozygous for the 1G-variant exhibited low levels of gene expression. Cells homozygous for the 2G-variant or heterozygous (1G/2G) had elevated levels of both mRNA and protein. These relative levels were also seen after CSC expo-sure. MMP-1 genotypes of 104 Caucasian males acquired from the Pathobiological Determinants of Atherosclerosis in Youth study were compared with the extent of atherosclerotic lesion development in the aorta. The results indicate that, although the MMP-1 SNP influences MMP-1 gene expression in cultured HAEC exposed to CSC, differences in lesion development were not observed based on this polymorphism in young Caucasian males.