Role of Endothelial Shear Stress in the Natural History of Coronary Atherosclerosis and Vascular Remodeling

Abstract

Although the entire coronary tree is exposed to the atherogenic effect of the systemic risk factors, atherosclerotic lesions form at specific arterial regions, where low and oscillatory endothelial shear stress (ESS) occur. Low ESS modulates endothelial gene expression through complex mechanoreception and mechanotransduction processes, inducing an atherogenic endothelial phenotype and formation of an early atherosclerotic plaque. Each early plaque exhibits an individual natural history of progression, regression, or stabilization, which is dependent not only on the formation and progression of atherosclerosis but also on the vascular remodeling response. Although the pathophysiologic mechanisms involved in the remodeling of the atherosclerotic wall are incompletely understood, the dynamic interplay between local hemodynamic milieu, low ESS in particular, and the biology of the wall is likely to be important. In this review, we explore the molecular, cellular, and vascular processes supporting the role of low ESS in the natural history of coronary atherosclerosis and vascular remodeling and indicate likely mechanisms concerning the different natural history trajectories of individual coronary lesions. Atherosclerotic plaques associated with excessive expansive remodeling evolve to high-risk plaques, because low ESS conditions persist, thereby promoting continued local lipid accumulation, inflammation, oxidative stress, matrix breakdown, and eventually further plaque progression and excessive expansive remodeling. An enhanced understanding of the pathobiologic processes responsible for atherosclerosis and vascular remodeling might allow for early identification of a high-risk coronary plaque and thereby provide a rationale for innovative diagnostic and/or therapeutic strategies for the management of coronary patients and prevention of acute coronary syndromes.

Extracellular Fluid Excess Is Significantly Associated With Coronary Artery Calcification in Patients With Chronic Kidney Disease

“…In endothelial cells, the biological response of this circumferential stretch promotes the release of angiotensin II and the activation of angiotensin II receptor 1, thereby enhancing superoxide production and reducing the bioavailability of nitric oxide 28, 29. This results in low, oscillating, or reversing shear stress, which in turn leads to atherosclerosis and vascular calcification 30, 31. VSMCs sense the disturbed wall shear stress and pressure distension caused by intravascular and interstitial fluid overload through membrane mechanoreceptors, and activate the signaling pathways such as small guanosine triphosphatase related to Ras A (RhoA)/Rho‐associated protein kinase, mitogen‐activated protein kinase, phosphatidylinositol‐3‐kinase/protein kinase B, and extracellular signal‐regulated kinase 32, 33, 34.…”

Myocardial bridges are free from atherosclerosis: Overview of the underlying mechanisms

“…It is defined as the product of the velocity gradient near the wall and the blood viscosity; this definition suggests that SS varies proportionally with flow. Low and oscillatory SS are characterized by low time-averaged values (less than 1.5 N/m 2 ) and significant variations in direction and magnitude over short distances, and constitute major determinants of the localization, development and progression of atherosclerosis (20)(21)(22)(23)(24). Through complex mechanotransduction processes similar to those initiated by TS, coronary endothelium responds to low and oscillatory SS by adopting a vasoconstrictive (ET-1), proinflammatory (adhesion molecules and cytokines), pro-oxidative, growth-promoting and prothrombotic phenotype, ultimately acquiring a predisposition to atherosclerosis (16,20,24).…”

“…Low and oscillatory SS are characterized by low time-averaged values (less than 1.5 N/m 2 ) and significant variations in direction and magnitude over short distances, and constitute major determinants of the localization, development and progression of atherosclerosis (20)(21)(22)(23)(24). Through complex mechanotransduction processes similar to those initiated by TS, coronary endothelium responds to low and oscillatory SS by adopting a vasoconstrictive (ET-1), proinflammatory (adhesion molecules and cytokines), pro-oxidative, growth-promoting and prothrombotic phenotype, ultimately acquiring a predisposition to atherosclerosis (16,20,24). On the other hand, the normal pulsatile SS, with a positive time-average ranging between 1.5 N/m 2 and 7.0 N/ m 2 , increases the production of nitric oxide and downregulates the expression of proatherogenic molecules, thereby conferring atheroprotection (16,20,24).…”

Shear stress increases cytotoxicity and reduces transfection efficiency of liposomal gene delivery to CHO-S cells

“…The effect of shear stress has been largely studied in adherent cells primarily due to interest in the effect of shear stress on endothelial cells in blood vessels, and is known to affect various aspects of cell physiology including cell morphology, size and metabolism (Chatzizisis et al 2007;Haga et al 2007;Heo et al 2012;Resnick et al 2003). In addition, shear stress is also known to affect cellular uptake of extracellular cargo.…”