Matrix ageing and vascular impacts: focus on elastin fragmentation

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and represent a major problem of public health. Over the years, life expectancy has considerably increased throughout the world, and the prevalence of CVD is inevitably rising with the growing ageing of the population. The normal process of ageing is associated with progressive deterioration in structure and function of the vasculature, commonly called vascular ageing. At the vascular level, extracellular matrix (ECM) ageing leads to molecular alterations in long half-life proteins, such as elastin and collagen, and have critical effects on vascular diseases. This review highlights ECM alterations occurring during vascular ageing with a specific focus on elastin fragmentation and also the contribution of elastin-derived peptides (EDP) in age-related vascular complications. Moreover, current and new pharmacological strategies aiming at minimizing elastin degradation, EDP generation, and associated biological effects are discussed. These strategies may be of major relevance for preventing and/or delaying vascular ageing and its complications.

Serum Concentrations of Endothelin-1 and Matrix Metalloproteinases-2, -9 in Pre-Hypertensive and Hypertensive Patients with Type 2 Diabetes

“…Furthermore, a chronic increase in MMP activation is central to age-associated arterial structural remodeling [81]. Throughout aging, the balance between MMPs and their inhibitors is changing [82] and MMP-2/-9 expression and activity are increased in vascular walls [83,84]. Typical vascular diseases such as hypertension and atherosclerosis also could be viewed as accelerated arterial aging and they are also linked to increased MMP activation [81].…”

Cell–cell junctional mechanotransduction in endothelial remodeling

“…Accumulation of advanced glycation end-products (AGEs) reinforces this process by increasing the crosslinking of collagen [130]. Elastin levels decrease in the vessel wall during aging, which is considered an irreversible process, underlying a large part of the stiffening process [131]. Besides such alterations in the ECM, changes in the activity and structure of vascular smooth muscle cells with aging promote vessel stiffness [132].…”

In Development—A New Paradigm for Understanding Vascular Disease

“…Stiffness is further enhanced by increased fragility and reduced compliance of aging elastin fibers and by increased crosslinking and resilience of collagen and fibronectin matrices (127, 150). The expression of key inflammatory and fibrotic mediators is localized predominantly to endothelial cells and intimal smooth muscle cells (SMCs), and appears to be coordinated by local generation of ANGII (135, 137, 139, 140, 148, 149, 151, 152).…”