Matrix Stiffness, Endothelial Dysfunction and Atherosclerosis

Abstract

Background Atherosclerosis (AS) is the leading cause of the human cardiovascular disease (CVDs). Endothelial dysfunction promotes the monocytes infiltration and inflammation that participate fundamentally in atherogenesis. Endothelial cells (EC) have been recognized as mechanosensitive cells and have different responses to distinct mechanical stimuli. Emerging evidence shows matrix stiffness-mediated EC dysfunction plays a vital role in vascular disease, but the underlying mechanisms are not yet completely understood. Methods It is through literature search to introduce the detailed role of matrix stiffness in the EC dysfunction in the process of AS diseases. Results This article aims to summarize the effect of matrix stiffness on the pro-atherosclerotic characteristics of EC including morphology, rigidity, biological behavior and function as well as the related mechanical signal. The review also discusses and compares the contribution of matrix stiffness-mediated phagocytosis of macrophages and EC to AS progression. Conclusion These advances in our understanding of the relationship between matrix stiffness and EC dysfunction open the avenues to improve the prevention and treatment of now-ubiquitous atherosclerotic diseases.

Mechanisms underlying TRPV4-mediated regulation of miR-146a expression

“…To validate our in vitro observations in a disease context, we induced atherosclerosis, a chronic inflammatory vascular disease associated with matrix stiffening (41), in ApoE KO mice by administering a high-fat diet (HFD) to create a hyperlipidemic condition. After 12 weeks, aortic root areas from both ApoE KO and ApoE:TRPV4 DKO mice, fed either a chow or HFD, were analyzed through IF-FISH assays.…”

“…The remodeling of the extracellular and intracellular matrix can alter arterial tissue stiffness, potentially initiating molecular pathways that contribute to atherogenesis (3, 21, 41). There’s growing evidence linking miR-regulating genes to the onset and progression of atherosclerosis, with miR-146a’s role being particularly debated (50).…”