Low-density lipoprotein-cholesterol-induced endothelial dysfunction and oxidative stress: the role of statins.
CONCLUSIONS
Cardiovascular diseases (CVD) represent a major public health burden. High low-density lipoprotein (LDL)-cholesterol is a recognized pathogenic factor for atherosclerosis, and its complications and statins represent the most potent and widely used therapeutic approach to prevent and control these disorders.


BACKGROUND
A number of clinical and experimental studies concur to identify endothelial dysfunction as a primary step in the development of atherosclerosis, as well as a risk factor for subsequent clinical events. Oxidant stress resulting from chronic elevation of plasma LDL-cholesterol (LDL-chol) is a major contributor to both endothelial dysfunction and its complications, for example, through alterations of endothelial nitric oxide signaling.


RESULTS
Statin treatment reduces morbidity and mortality of CVD, but increasing evidence questions that this is exclusively through reduction of plasma LDL-chol. The identification of ancillary effects on (cardio)vascular biology, for example, through their modulation of oxidative stress, will not only increase our understanding of their mechanisms of action, with a potential broadening of their indication(s), but also lead to the identification of new molecular targets for future therapeutic developments in CVD.


CONCLUSIONS
Further characterization of molecular pathways targeted by statins, for example, not directly mediated by changes in plasma lipid concentrations, should enable a more comprehensive approach to the pathogenesis of (cardio)vascular disease, including, for example, epigenetic regulation and fine tuning of cell metabolism.
1 Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain , Brussels, Belgium .
Nerea
N
Hermida
Jean-Luc
JL
Balligand
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D008078:Cholesterol, LDL / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction
D000893:Anti-Inflammatory Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III