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Cardiovasc Res. 2018 Jan 1;114(1):35-52. doi: 10.1093/cvr/cvx226.

Endothelial permeability, LDL deposition, and cardiovascular risk factors-a review.

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Department of Biological and Environmental Science and Technology (DISTEBA), University of Salento, via Monteroni, 73100, Lecce, Italy.
National Research Council (CNR), Department of Biomedical sciences, Institute of Clinical Physiology, Via Monteroni, 73100, Lecce, Italy.
Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat, NL-1081 BT, Amsterdam, The Netherlands.
Department of Molecular, Cell and Developmental Biology and Molecular Biology Institute, University of California, 610 Charles E Young Dr S, 90095, Los Angeles, USA; and.
Department of Neuroscience, Imaging and Clinical Science and Institute of Advanced Biomedical Technologies, University G. D'Annunzio, via dei Vestini, 66100 Chieti, Italy.


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.


Atherosclerosis; Cardiovascular risk factors; Endothelium; Vascular permeability

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