Extracellular Matrix in Aging Aorta

Abstract

The aging population is booming all over the world and arterial aging causes various age-associated pathologies such as cardiovascular diseases (CVDs). The aorta is the largest elastic artery, and transforms pulsatile flow generated by the left ventricle into steady flow to maintain circulation in distal tissues and organs. Age-associated structural and functional changes in the aortic wall such as dilation, tortuousness, stiffening and losing elasticity hamper stable peripheral circulation, lead to tissue and organ dysfunctions in aged people. The extracellular matrix (ECM) is a three-dimensional network of macromolecules produced by resident cells. The composition and organization of key ECM components determine the structure-function relationships of the aorta and therefore maintaining their homeostasis is critical for a healthy performance. Age-associated remodeling of the ECM structural components, including fragmentation of elastic fibers and excessive deposition and crosslinking of collagens, is a hallmark of aging and leads to functional stiffening of the aorta. In this mini review, we discuss age-associated alterations of the ECM in the aortic wall and shed light on how understanding the mechanisms of aortic aging can lead to the development of efficient strategy for aortic pathologies and CVDs.

Keywords: aging; aorta; collagen; elastin; extracellular matrix; stiffness.

FIGURE 1

ECM structures and cellular components in the aortic wall. Young aortic wall (left): In intima, endothelial cells (ECs) maintain homeostasis of the wall by forming seamless barrier structure over the basement membrane (BM) and producing vasoprotective factors such as nitric oxide (NO). In media, key ECM molecules (e.g., elastin, collagen) and vascular smooth muscle cells (VSMCs) create the contractile units to maintain vascular tone and compliance. In adventitia, collagen fibers support the aortic wall to prevent overexpansion, and various adventitial cellular and non-cellular ECM components maintain homeostasis of the aortic wall. Aged aortic wall (right): Aging induces senescence of the ECs, which leads to chronic low-grade inflammation and subsequent aberrant ECM remodeling (fragmentation of elastin, excess deposition of collagen and their crosslinking) in the intima and media. Adventitial fibroblasts directly or indirectly stiffen the aortic wall by depositing excessive collagens.

FIGURE 2

Changes in aortic functions during aging. Aortic wall stores energy generated by the left ventricle during systole and release the energy during diastole by returning to its initial dimension. This facilitates smooth and constant circulation in the peripheral tissues and organs (top). Aged aorta becomes dilated and tortuous. Together with these morphological changes, thickening and stiffening of the aging aortic wall disturb the local circulation, which leads to the tissue and organ dysfunction (bottom).