Large elastic artery stiffness with aging: novel translational mechanisms and interventions

Abstract

Large elastic artery stiffness is an independent predictor of age-related cardiovascular events that is attributable to structural remodeling throughout the artery. The intima, media and adventitial layers of the artery uniquely remodel with advancing age and all contribute to arterial stiffening. The specific expression of the extracellular matrix proteins collagen and elastin, and post-translational modifications of these proteins by advanced glycation end-products are key mechanisms in arterial stiffening with age and will be reviewed in the context of region-specific expression. In addition, interventions for attenuating age-related arterial stiffness and novel imaging advances for translating basic findings to older clinical populations will be discussed.

Keywords: Advanced glycation endproducts; Adventitia; Collagen; Elastin; Intima; Media; inflammation; oxidative stress.

Figure 1

Summary of region-specific modifications with age and proposed mechanisms contributing to artery stiffness. Aging results in greater oxidative stress and inflammation that promotes region specific remodeling in the intimal, medial and adventitial layers that contributes to arterial stiffening. The intima has greater collagen, smooth muscle alpha actin (SMαA) and advanced glycation endproduct (AGEs) expressions. The increased SMαA may be a result of smooth muscle cell migration from the media or a novel endothelial phenotypic change. Within the medial layer collagen and AGEs accumulation are greater, whereas elastin is reduced. The elastin modulating enzymes Lysyl Oxidase (LOX) and matrix metalloproteinase-2 (MMP-2) are also modulated in the media to promote elastin degradation. Adventitial transforming growth factor beta 1 (TGF-β1), myofibroblasts, collagen and AGEs expressions are greater. TGF-β1 induces a myofibroblast phenotype and collagen in fibroblasts.