The role of oxidized low-density lipoproteins in atherosclerosis: the myths and the facts.
The oxidative modification hypothesis of atherosclerosis, which assigns to oxidized low-density lipoproteins (LDLs) a crucial role in atherosclerosis initiation and progression, is still debated. This review examines the role played by oxidized LDLs in atherogenesis taking into account data derived by studies based on molecular and clinical approaches. Experimental data carried out in cellular lines and animal models of atherosclerosis support the proatherogenic role of oxidized LDLs: (a) through chemotactic and proliferating actions on monocytes/macrophages, inciting their transformation into foam cells; (b) through stimulation of smooth muscle cells (SMCs) recruitment and proliferation in the tunica intima; (c) through eliciting endothelial cells, SMCs, and macrophages apoptosis with ensuing necrotic core development. Moreover, most of the experimental data on atherosclerosis-prone animals benefiting from antioxidant treatment points towards a link between oxidative stress and atherosclerosis. The evidence coming from cohort studies demonstrating an association between oxidized LDLs and cardiovascular events, notwithstanding some discrepancies, seems to point towards a role of oxidized LDLs in atherosclerotic plaque development and destabilization. Finally, the results of randomized clinical trials employing antioxidants completed up to date, despite demonstrating no benefits in healthy populations, suggest a benefit in high-risk patients. In conclusion, available data seem to validate the oxidative modification hypothesis of atherosclerosis, although additional proofs are still needed.
Department of Medicine (DIMED), Internal Medicine 4, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
Giuseppe
G
Maiolino
Giacomo
G
Rossitto
Paola
P
Caielli
Valeria
V
Bisogni
Gian Paolo
GP
Rossi
Lorenzo A
LA
Calò
D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D050197:Atherosclerosis / Q000378:metabolism*; D049109:Cell Proliferation; D002633:Chemotaxis; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D009336:Necrosis; D018384:Oxidative Stress; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D017539:Tunica Intima / Q000378:metabolism
D000975:Antioxidants; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein