Endothelial–Vascular Smooth Muscle Cells Interactions in Atherosclerosis

Abstract

Atherosclerosis is a chronic progressive inflammatory process that can eventually lead to cardiovascular disease (CVD). Despite available treatment, the prevalence of atherosclerotic CVD, which has become the leading cause of death worldwide, persists. Identification of new mechanisms of atherogenesis are highly needed in order to develop an effective therapeutic treatment. The blood vessels contain two primary major cell types: endothelial cells (EC) and vascular smooth muscle cells (VSMC). Each of these performs an essential function in sustaining vascular homeostasis. EC-VSMC communication is essential not only to development, but also to the homeostasis of mature blood vessels. Aberrant EC-VSMC interaction could promote atherogenesis. Identification of the mode of EC-VSMC crosstalk that regulates vascular functionality and sustains homeostasis may offer strategic insights for prevention and treatment of atherosclerotic CVD. Here we will review the molecular mechanisms underlying the interplay between EC and VSMC that could contribute to atherosclerosis. We also highlight open questions for future research directions.

Endothelial TGF-β signaling instructs smooth muscle development in the cardiac outflow tract

“…In particular, ALK5 in pericytes interferes with ECM degradation processes, leading to an EC hyperproliferation state (Dave et al, 2018). Moreover, defective interactions between ECs and SMCs have been implicated in different pathologies including pulmonary hypertension, atherosclerosis and arteriovenous malformations (e.g., hereditary hemorrhagic telangiectasia) (Mancini et al, 2009; Gao et al, 2016; Cunha et al, 2017; Li et al, 2018).…”

“…The communication between ECs and SMCs can be carried out in different ways, such as physical contact, exchange of signaling cues and ECM deposition (Gaengel et al, 2009; Lilly, 2014; Li et al, 2018; Sweeney and Foldes, 2018), all of which are likely to play a role in alk5 mutant phenotype. In addition, during development, SMCs are recruited to the vessels once the initial establishment of the endothelial layer is completed (Stratman et al, 2017; Sweeney and Foldes, 2018).…”

Long non‐coding RNA SNHG16 regulates human aortic smooth muscle cell proliferation and migration via sponging miR‐205 and modulating Smad2

“…The pathogenesis of atherosclerosis involves both genetic and environmental factors, and the abnormal cellular behaviours of VSMCs are believed to be the main contributor to the development of atherosclerosis. 4 Therefore, identifying novel genes or signalling pathway for VSMC proliferation and migration is a reasonable strategy to provide better solutions for the treatment of atherosclerosis. In The lncRNA SNHG16 has been implicated for its important roles in regulating cancer progression, and various molecular mechanisms for SNHG16 were also proposed.…”

“…Cardiovascular diseases (CVDs) such as atherosclerosis are the leading cause of death globally . The aberrant proliferation of vascular smooth muscle cells (VSMCs) plays the essential role in the pathogenesis of CVDs such as the development of atherosclerotic plaque . Platelet‐derived growth factor (PDGF) exists as three isoforms including PDGF‐aa, PDGF‐ab and PDGF‐bb .…”

“…1,2 The aberrant proliferation of vascular smooth muscle cells (VSMCs) plays the essential role in the pathogenesis of CVDs such as the development of atherosclerotic plaque. 3,4 Platelet-derived growth factor (PDGF) exists as three isoforms including PDGF-aa, PDGF-ab and PDGF-bb. 5,6 Studies have found that PDGF-bb is overexpressed in the VSMCs in the atherosclerotic regions, and PDGF-bb inhibition reduces the size of atherosclerotic lesion.…”