title: Dual role of lipoproteins in endothelial cell dysfunction in atherosclerosis.
abstract: The endothelium is a key constituent of the vascular wall, being actively involved in maintaining the structural integrity and proper functioning of blood vessels. Hyperlipidemia, diabetes, hypertension, smoking and aging are important risk factors for the dysfunction of endothelial cells (EC). Circulating lipoproteins (Lp) synthesized and secreted from the intestine or liver have an important role in supplying peripheral tissues with fatty acids from triglyceride rich lipoproteins (TGRLp) for energy production or storage, and cholesterol from low density lipoproteins (LDL) or high density lipoproteins (HDL) for the synthesis of cellular membranes and steroid hormones. Under pathological conditions, Lp may suffer alterations in concentration and composition and become aggressors for EC. Modified LDL, remnant Lp, TGRLp lipolysis products, dysfunctional HDL are involved in the changes induced in EC morphology (reduced glycocalyx, overdeveloped endoplasmic reticulum, Golgi apparatus and basement membrane), loose intercellular junctions, increased oxidative and inflammatory stress, nitric oxide/redox imbalance, excess Lp transport and storage, as well as loss of anti-thrombotic properties, all of these being characteristics of endothelial dysfunction. Normal HDL are able to counteract the harmful effects of atherogenic Lp in EC but under persistent pathological conditions they lose the protective properties and become pro-atherogenic. This review summarises recent advances in understanding the role of Lp in the induction of endothelial dysfunction and the initiation and progression of atherosclerotic lesions. Its main focus is the antagonistic role of atherogenic Lp (LDL, VLDL, dysfunctional HDL) versus anti-atherogenic Lp (HDL), also pointing out the potential targets for arresting or reversing this process.
authors.affiliation: Institute of Cellular Biology and Pathology Nicolae Simionescu of the Romanian Academy, 8, B.P.Hasdeu Street, 050568 Bucharest, Romania.
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Stancu
authors.forename: Laura
authors.initials: L
authors.lastname: Toma
authors.forename: Anca V
authors.initials: AV
authors.lastname: Sima
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress
chemical_list: D016207:Cytokines; D008074:Lipoproteins