Abstract | SIGNIFICANCE: RECENT ADVANCES: In the last decade, the concept of statin pleiotropy has been reinforced by a large number of cell culture, animal, and translational studies. Statins have been shown to suppress the activity of pro-oxidant enzymes (such as NADPH oxidase) and pro-inflammatory transcriptional pathways in the endothelium. At the same time, they enhance endothelial NO synthase expression and activity while they also improve its enzymatic coupling. This leads to increased NO bioavailability and improved endothelial function. CRITICAL ISSUES: Despite significant recent advances, the exact mechanisms of statin pleitropy are still only partially understood. The vast majority of the published literature relies on animal studies, while the actual mechanistic studies in humans are limited. FUTURE DIRECTIONS: The success of statins as endothelium redox-modifying agents with a direct impact on clinical outcome highlights the importance of the endothelium as a therapeutic target in CVD. Better understanding of the mechanisms that underlie endothelial dysfunction could lead to the design of novel therapeutic strategies that target the vascular endothelium for the prevention and treatment of CVD.
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Authors | Marios Margaritis, Keith M Channon, Charalambos Antoniades |
Journal | Antioxidants & redox signaling
(Antioxid Redox Signal)
Vol. 20
Issue 8
Pg. 1198-215
(Mar 10 2014)
ISSN: 1557-7716 [Electronic] United States |
PMID | 24111702
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Reactive Oxygen Species
- NOS3 protein, human
- Nitric Oxide Synthase Type III
- NADPH Oxidases
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Topics |
- Animals
- Atherosclerosis
(drug therapy, metabolism)
- Endothelium, Vascular
(drug effects, metabolism)
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(adverse effects, pharmacology, therapeutic use)
- NADPH Oxidases
(metabolism)
- Nitric Oxide Synthase Type III
(metabolism)
- Oxidation-Reduction
- Oxidative Stress
(drug effects)
- Reactive Oxygen Species
(metabolism)
- Transcriptome
(drug effects)
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