Structural and Genetic Bases of Arterial Stiffness

Abstract

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.

Compliance and pulse wave velocity assessed by MRI detect early aortic impairment in young patients with mutation of the smooth muscle myosin heavy chain

“…Noninvasive evaluation of aortic stiffness could be useful for risk assessment and preventive follow-up strategy in young asymptomatic relatives of subjects with other aortic inherited diseases, such as Marfan syndrome, Ehlers-Danlos syndrome, or other syndromic or nonsyndromic familial forms of thoracic aneurysm and dissection. In monogenic connective tissue diseases, arterial stiffness is directly affected by genetic determinants (38). Our results converge with other studies performed on the Marfan syndrome and vascular Ehlers-Danlos (4,16).…”

Regional Cerebral Blood Flow and Arterial Blood Volume and Their Reactivity to Hypercapnia in Hypertensive and Normotensive Rats

“…Both CBF and CBV a were obtained from exactly the same data sets using equations (1) and (2), respectively. Cerebral blood flow was calculated from the slope, whereas CBV a was determined primarily from the intercept of linear fitting, as the slope is much less than 2a a in equation (2). As only two points were used for fitting, fitting errors could not be determined.…”

Fish oil supplementation improves large arterial elasticity in overweight hypertensive patients

“…Arterial wall properties are also influenced by functional characteristics such as the tonicity of the artery or changes in pressure (Laurent et al, 2005). The rapidity with which fish oil improved arterial elasticity indicates an effect on the functional components that determine elasticity.…”