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Genetics and pathophysiology of arterial stiffness

Abstract

Arterial stiffness is a cardiovascular risk factor that is independent of arterial pressure. Clinically, carotid-femoral pulse wave velocity (PWV) is the gold-standard parameter of arterial stiffness. Recent genetic studies have revealed specific genes that contribute to arterial stiffening. Here we review the recent findings on genome-wide linkage analyses and candidate gene polymorphism association studies. We also focus on the latest advances in the identification of gene variants affecting PWV using high density array single nucleotide polymorphism technology in a recent genome-wide association (GWA) study. Linkage and polymorphism studies revealed a first group of genes affecting the renin–angiotensin–aldosterone system, elastic fibre structural components, metalloproteinases, and the NO pathway. A second group of genes, identified by polymorphism association studies and possibly involved in the pathophysiology of arterial stiffness, includes β-adrenergic receptors, endothelin receptors, and inflammatory molecules. The last group of genes, identified by GWA studies and unrelated to currently suspected mechanisms of arterial stiffness, may target transcriptional pathways controlling gene expression, differentiation of vascular smooth muscle cells, apoptosis of endothelial cells, or the immune response within the vascular wall.

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    1. Cardiovasc Res (2009) 81 (4): 637-648. doi: 10.1093/cvr/cvn353 First published online: December 20, 2008
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