The role of shear stress in the generation of rupture-prone vulnerable plaques

Abstract

Blood-flow-induced shear stress acting on the arterial wall is of paramount importance in vascular biology. Endothelial cells sense shear stress and largely control its value in a feedback-control loop by adapting the arterial dimensions to blood flow. Nevertheless, to allow for variations in arterial geometry, such as bifurcations, shear stress control is modified at certain eccentrically located sites to let it remain at near-zero levels. In the presence of risk factors for atherosclerosis, low shear stress contributes to local endothelial dysfunction and eccentric plaque build up, but normal-to-high shear stress is atheroprotective. Initially, lumen narrowing is prevented by outward vessel remodeling. Maintenance of a normal lumen and, by consequence, a normal shear stress distribution, however, prolongs local unfavorable low shear stress conditions and aggravates eccentric plaque growth. While undergoing such growth, eccentric plaques at preserved lumen locations experience increased tensile stress at their shoulders making them prone to fissuring and thrombosis. Consequent loss of the plaque-free wall by coverage with thrombus and new tissue may bring shear-stress-controlled lumen preservation to an end. This change causes shear stress to increase, which as a new condition may transform the lesion into a rupture-prone vulnerable plaque. We present a discussion of the role of shear stress, in setting the stage for the generation of rupture-prone, vulnerable plaques, and how this may be prevented.

Plaque Location in the Left Anterior Descending Coronary Artery and Tissue Characteristics in Angina Pectoris: An Integrated Backscatter Intravascular Ultrasound Study

“…21,22 The role of systemic factors such as inflammation 6 and lowdensity lipoprotein cholesterol 7 in the development of plaque vulnerability has been well documented. Recent interest has focused on the role of local factors, such as shear stress, in the development of high-risk coronary sites 5,23 and the genesis and progression of coronary atherosclerotic lesions. Atherosclerotic lesions predominantly occur in curved arteries and near side branches where wall shear stress is low.…”

“…Pathophysiologically, low shear stress is thought to induce loss of the physiologic floworiented alignment of endothelial cells, thereby increasing the expression of adhesion molecules and weakening cell junctions, ultimately leading to increased permeability of vascular tissue to lipids and macrophages. 5,[28][29][30] …”

“…1,2 Epidemiological studies of patients with ST-segment elevation myocardial infarction have reported that the sites of occlusion and plaque rupture are not uniformly distributed throughout each major coronary artery, but tended to cluster within the proximal segments of these vessels, especially within the first 30 mm from the ostium of the left anterior descending coronary artery (LAD). 3,4 Several mechanisms have been proposed to explain this phenomenon, such as shear stress, 5 inflammation, 6 and oxidative stress, 7 but it remains speculative. Pathological studies have suggested that the tissue characteristics of coronary plaque are an important determinant of vulnerability.…”

Hemodynamics analyses in treated and untreated carotid arteries of the same patient: A preliminary study based on three patient cases

“…It is reported that high values of TGWSS over 35.5 Pa/s are related to the expression of atherogenesisrelated genes in endothelial cells [25,26]. This may indicate the vulnerability of the narrowing regions that may potentially suffer from atherosclerosis.…”

“…WSS is reported to be related to endothelial cell function and is an important factor in the progression of atherosclerosis [21,22]. High WSS over 30 Pa may induce desquamation of endothelial cells, platelet aggregation, intimal injury or rupture of vulnerable plaques [23,24]. The WSS distributions in all of the cases are below 30Pa, except for the stenosis at the carotid bulb and the proximal ICA of PIII.…”