title: Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis.
abstract: Atherosclerosis is a progressive disease in which endothelial cell dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation, lead to the loss of vascular homeostasis. Oxidized low-density lipoprotein (oxLDL) may play a pre-eminent function in atherosclerotic lesion formation, even if their role is still debated. Several types of scavenger receptors (SRs) such as SR-AI/II, SRBI, CD36, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), toll-like receptors (TLRs) and others can promote the internalization of oxLDL. They are expressed on the surface of vascular wall cells (endothelial cells, macrophages and smooth muscle cells) and they mediate the cellular effects of oxLDL. The key influence of both oxLDL and SRs on the atherogenic process has been established in atherosclerosis-prone animals, in which antioxidant treatment and/or silencing of SRs has been shown to reduce atherogenesis. Despite some discrepancies, the indication from cohort studies that there is an association between oxLDL and cardiovascular (CV) events seems to point toward a role for oxLDL in atherosclerotic plaque progress and disruption. Finally, randomized clinical trials using antioxidants have demonstrated benefits only in high-risk patients, suggesting that additional proofs are still needed to better define the involvement of each type of modified LDL in the development of atherosclerosis.
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti-Pescara, Italy; Aging Research Center, Ce.S.I., "G. d'Annunzio" University Foundation, Chieti, Italy. Electronic address: n.dipietro@unich.it.
authors.forename: Natalia
authors.initials: N
authors.lastname: Di Pietro
authors.affiliation: Department of Medicine and Aging Sciences, University "G. d'Annunzio", Chieti-Pescara, Italy. Electronic address: gloria.formoso@unich.it.
authors.forename: Gloria
authors.initials: G
authors.lastname: Formoso
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio", Chieti-Pescara, Italy; Aging Research Center, Ce.S.I., "G. d'Annunzio" University Foundation, Chieti, Italy. Electronic address: assunta.pandolfi@unich.it.
authors.forename: Assunta
authors.initials: A
authors.lastname: Pandolfi
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein
keywords: Atherosclerosis; Macrophages; Oxidized low-density lipoproteins