Age-associated proinflammatory elastic fiber remodeling in large arteries

Abstract

Elastic fibers are the main components of the extracellular matrix of the large arterial wall. Elastic fiber remodeling is an intricate process of synthesis and degradation of the core elastin protein and microfibrils accompanied by the assembly and disassembly of accessory proteins. Age-related morphological, structural, and functional proinflammatory remodeling within the elastic fiber has a profound effect upon the integrity, elasticity, calcification, amyloidosis, and stiffness of the large arterial wall. An age-associated increase in arterial stiffness is a major risk factor for the pathogenesis of diseases of the large arteries such as hypertensive and atherosclerotic vasculopathy. This mini review is an update on the key molecular, cellular, functional, and structural mechanisms of elastic fiber proinflammatory remodeling in large arteries with aging. Targeting structural and functional integrity of the elastic fiber may be an effective approach to impede proinflammatory arterial remodeling with advancing age.

Keywords: Aging; Elastic fibers; Large artery; Proinflammation.

Figure 1.

Step by step illustration of proposed micro-and macro-assembly of elastic fibers known as elastogenesis, referred from previous reports (NivisoŽ Smith and Weiss, 2011; Pshezhetsky and Hinek, 2009; Schmelzer et al., 2020). (1) Tropoelastin is transcribed and translated from the ELN gene and is soluble and fragile. (2) Tropoelastin binds to EBP, limiting self-aggregation and degradation, and is secreted from vascular elastogenic cells; (3) Tropoelastin is released at the cell surface through competition by galactosugars in the microfibrils. Released tropoelastin is aligned and coacervated on the microfibrils while released EBP is eventually recycled back into the cell. (4) Fibulin binds tropoelastin aggregates and stabilize them. (5) LOX on the microfibrils processes tropoelastin in the extracellular space, which polymerizes tropoelastin to form mature insoluble ELN through desmosine and isodesmosine cross-links. (6) Finally, the elastic fiber is assembled, which consists of a core of ELN surrounded by microfibrils.

Figure 2.

Elastic fiber remodeling and the aging vascular wall. A. Representative photomicrographs of EVG elastic staining in aortic walls from young (2mo, left) and old (30 mo, right) Fisher 344 cross-bred rats (FXBN), modified from previous finding (Wang and Lakatta, 2002). B. A list of adverse remodeling events in large aging arterial walls.