title: Structural and genetic bases of arterial stiffness.
abstract: Arterial stiffness has independent predictive value for cardiovascular events. We review data concerning the heritability of arterial stiffness, and propose an integrated view of the structural and genetic determinants of arterial stiffness, based on a candidate gene approach and recent studies on gene expression profile. Arterial stiffness seems to have a genetic component, which is largely independent of the influence of blood pressure and other cardiovascular risk factors. In animal models of essential hypertension (SHR and SHR-SP), structural modifications of the arterial wall include an increase in the number of elastin/smooth muscle cell (SMC) connections, and smaller fenestrations of the internal elastic lamina, possibly leading to redistribution of the mechanical load toward elastic materials. These modifications may give rise to mechanisms that explain why changes in arterial wall material accompanying wall hypertrophy in these animals are not associated with an increase in arterial stiffness. In monogenic connective tissue diseases (Marfan, Williams, and Ehlers-Danlos syndromes) and the corresponding animal models, precise characterization of the arterial phenotype makes it possible to determine the influence of abnormal genetically determined wall components on arterial stiffness. Such studies have highlighted the role of extracellular matrix signaling in the vascular wall and have shown that elastin and collagen not only display elasticity or rigidity but also are involved in the control of SMC function. These data provide strong evidence that arterial stiffness is affected by the amount and density of stiff wall material and the spatial organization of that material.
authors.affiliation: Department of Pharmacology and INSERM EMI 107, Hôpital Européen Georges Pompidou, Paris, France. stephane.laurent@egp.ap-hop-paris.fr
authors.forename: Stéphane
authors.initials: S
authors.lastname: Laurent
authors.forename: Pierre
authors.initials: P
authors.lastname: Boutouyrie
authors.forename: Patrick
authors.initials: P
authors.lastname: Lacolley
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology* / Q000503:physiopathology*; D003187:Compliance; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D014652:Vascular Diseases / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy