Role of elastin peptides and elastin receptor complex in metabolic and cardiovascular diseases

Abstract

The Cardiovascular Continuum describes a sequence of events from cardiovascular risk factors to end‐stage heart disease. It includes conventional pathologies affecting cardiovascular functions such as hypertension, atherosclerosis or thrombosis and was traditionally considered from the metabolic point of view. This Cardiovascular Continuum, originally described by Dzau and Braunwald, was extended by O'Rourke to consider also the crucial role played by degradation of elastic fibers, occurring during aging, in the appearance of vascular stiffness, another deleterious risk factor of the continuum. However, the involvement of the elastin degradation products, named elastin‐derived peptides, to the Cardiovascular Continuum progression has not been considered before. Data from our laboratory and others clearly showed that these bioactive peptides are central regulators of this continuum, thereby amplifying appearance and evolution of cardiovascular risk factors such as diabetes or hypertension, of vascular alterations such as atherothrombosis and calcification, but also nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The Elastin Receptor Complex has been shown to be a crucial actor in these processes. We propose here the participation of these elastin‐derived peptides and of the Elastin Receptor Complex in these events, and introduce a revisited Cardiovascular Continuum based on their involvement, for which elastin‐based pharmacological strategies could have a strong impact in the future.

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

“…Thus, ECM is an important niche component in regulation of cell behavior, including cell adhesion, proliferation and differentiation (Cramer and Badylak, 2019;Padhi and Nain, 2020). The effects of selected ECM components may depend on their molecular weight (Garantziotis and Savani, 2019;Wahart et al, 2019) and tissue specificity (Smith and Gerecht, 2018;Padhi and Nain, 2020).…”

Transmembrane Peptides as a New Strategy to Inhibit Neuraminidase-1 Activation

“…More recently, desialylation of platelets by NEU1 has been shown to play critical role in platelet clearance and thrombocytopenia (Li et al, 2015). At the plasma membrane, NEU1 is also involved in the modulation of elastic fiber assembly (Hinek et al, 2006) and the biological effects mediated by the elastin-derived peptides (Wahart et al, 2019). NEU1 and its chaperone (PPCA) were both identified as components of the elastin receptor complex together with the elastin-binding protein (Hinek et al, 2006).…”

Effects of Milk Fat Globule Epidermal Growth Factor VIII On Age-Associated Arterial Elastolysis, Fibrosis, and Calcification

“…The age-associated increases in arterial elastolysis is linked closely to an increase in arterial calcification [1][2][3][4] . Maintaining certain levels of intact TPELN is a key to ensuring arterial elastic meshwork integrity and arterial health 5,6,13 .…”

“…Aging is the major risk factor for quintessential cardiovascular diseases, such as hypertension, due mainly to adverse arterial proinflammatory remodeling [1][2][3] . With advancing age, the arterial wall becomes less resilient and stiffens, resulting mainly from a cascade of the breakdown and calcification of the elastic network, and from the proinflammation of vascular smooth muscle cells (VSMCs) [1][2][3][4][5][6][7][8] .…”