Elastin, arterial mechanics, and cardiovascular disease

Abstract

Large, elastic arteries are composed of cells and a specialized extracellular matrix that provides reversible elasticity and strength. Elastin is the matrix protein responsible for this reversible elasticity that reduces the workload on the heart and dampens pulsatile flow in distal arteries. Here, we summarize the elastin protein biochemistry, self-association behavior, cross-linking process, and multistep elastic fiber assembly that provide large arteries with their unique mechanical properties. We present measures of passive arterial mechanics that depend on elastic fiber amounts and integrity such as the Windkessel effect, structural and material stiffness, and energy storage. We discuss supravalvular aortic stenosis and autosomal dominant cutis laxa-1, which are genetic disorders caused by mutations in the elastin gene. We present mouse models of supravalvular aortic stenosis, autosomal dominant cutis laxa-1, and graded elastin amounts that have been invaluable for understanding the role of elastin in arterial mechanics and cardiovascular disease. We summarize acquired diseases associated with elastic fiber defects, including hypertension and arterial stiffness, diabetes, obesity, atherosclerosis, calcification, and aneurysms and dissections. We mention animal models that have helped delineate the role of elastic fiber defects in these acquired diseases. We briefly summarize challenges and recent advances in generating functional elastic fibers in tissue-engineered arteries. We conclude with suggestions for future research and opportunities for therapeutic intervention in genetic and acquired elastinopathies.

Constitutive interpretation of arterial stiffness in clinical studies: a methodological review

“…2C), the above studies reportedly did not assess underlying changes in collagen substructure. An extensive topical review on elastin in the context of arterial mechanics and cardiovascular disease has been published recently by Cocciolone et al (27). Focused reviews on medial calcification/elastocalcinosis are given by Atkinson (6) and Lanzer et al (75).…”

“…For other measures, e.g., carotid DC, the cardio-ankle vascular index, and brachial-ankle PWV, no risk score thresholds have been established or recommended yet. In contrast, arterial stiffness measurements in an (interventional) study context invariably evoke mechanistic interpretation, where measured changes are considered in relation to the existing knowledge and insights at the level of the extracellular matrix (ECM) and smooth muscle cells (27,46,73,77). In the last decade, a vast knowledge base has been developing from the molecular scale and genetic level toward the mechanobiological and biomechanical interactions between cells and the ECM (31,58,66).…”

A new finite‐element shell model for arterial growth and remodeling after stent implantation

“…Vascular tissues, as other biological tissues, commonly maintain homeostatic conditions during routine function; therefore, they continually adapt to any mechanical and biochemical alteration in their surrounding. Any factor disturbing the preferred homeostatic state of arterial wall, such as permanent hypertension or disruption of elastin fibers, may induce vascular growth and remodeling (G&R) which is a vital process to maintain vessel function. At the tissue scale, this manifests through continuous mass changes of the existent components in the extracellular matrix (ECM) such as collagen, elastin, and proteoglycans .…”

Nanoparticle-based targeted delivery of pentagalloyl glucose reverses elastase-induced abdominal aortic aneurysm and restores aorta to the healthy state in mice

“…Elastin is found in the major blood vessels of nearly all vertebrates formed of a pulsatile, high-pressure closed circulatory system 21 . Elastic fiber imparts reversible distensibility to the large arteries, allowing the aorta to deform during cyclic hemodynamic loading, with no permanent deformation or energy dissipation upon load retrieval 22 . One of the significant consequences of aneurysm development is degradation elastic lamina.…”