Endothelial permeability, LDL deposition, and cardiovascular risk factors—a review

Abstract

Early atherosclerosis features functional and structural changes in the endothelial barrier function that affect the traffic of molecules and solutes between the vessel lumen and the vascular wall. Such changes are mechanistically related to the development of atherosclerosis. Proatherogenic stimuli and cardiovascular risk factors, such as dyslipidaemias, diabetes, obesity, and smoking, all increase endothelial permeability sharing a common signalling denominator: an imbalance in the production/disposal of reactive oxygen species (ROS), broadly termed oxidative stress. Mostly as a consequence of the activation of enzymatic systems leading to ROS overproduction, proatherogenic factors lead to a pro-inflammatory status that translates in changes in gene expression and functional rearrangements, including changes in the transendothelial transport of molecules, leading to the deposition of low-density lipoproteins (LDL) and the subsequent infiltration of circulating leucocytes in the intima. In this review, we focus on such early changes in atherogenesis and on the concept that proatherogenic stimuli and risk factors for cardiovascular disease, by altering the endothelial barrier properties, co-ordinately trigger the accumulation of LDL in the intima and ultimately plaque formation.

Coronary artery plaque growth: A two‐way coupled shear stress–driven model

“…Second, WSS vectors are correlated to near‐wall biochemical accumulation. Transport and accumulation of certain biochemicals and labile agonist near the wall induce indirect EC mechanotransduction, and near‐wall accumulation of LDL promotes atherosclerosis . Prior work has shown a positive correlation between low WSS and LDL surface concentration, which has been explained by our work on Lagrangian WSS structures .…”

PCSK9 inhibition and inflammation: A narrative review

“…These areas express adhesion molecules and inflammatory genes to a higher extent [15]. In vessels with compromised glycocalyx, LDL penetrate the arterial intima via endothelial vesicles (transcytosis) or open endothelial junctions [16]. Lipoproteins < 70 nm in diameter, i.e.…”

Foam cell formation and cholesterol trafficking and metabolism disturbances in atherosclerosis

“…lipid accumulation in the arterial intima is known as fatty streaks -the earliest macroscopically visible stage of atherosclerosis. 5 At the microscopic level, these lesions are characterized by the presence of aggregated lipoprotein particles and cholesterol crystals in the affected cells, as demonstrated by 3D electron microscopy of human carotid atherosclerotic plaques. 6 the surface of the endothelial cells is covered by glycocalyx composed of glycoproteins, proteoglycans, and hyaluronan, which is the first barrier of the endothelial wall for lDl and other circulating agents.…”