The Pleiotropic Effects of the Hydroxy-Methyl-Glutaryl-CoA Reductase Inhibitors in Cardiovascular Disease

Abstract

The hydroxy-methyl-glutaryl-CoA reductase inhibitors (statins) are used extensively in the treatment of hyperlipidemia, and in the long-term prevention of coronary artery disease and stroke. They have also demonstrated a benefit in a variety of other cardiovascular disease processes. These secondary actions are known as pleiotropic effects. An updated discussion on the pleiotropy of statins is provided, and emphasizes the importance of randomized, placebo-controlled trials to further elucidate the potential benefits of these non-lipid-lowering actions in the treatment of cardiovascular disease.

Role of Micro-RNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells

“…Although miR-222 expression was not modified by ezetimibe in our work, the differences in the cellular models should be considered in this divergence. Moreover, the reduction of isoprenoids synthesis by statins -described as the main mechanism by which these drugs could exert their anti-inflammatory effects 9 -could also influence the differences observed between inhibitors of synthesis and absorption of cholesterol on endothelial NO modulation observed in this study. On the other hand, the observed reduction of miR-221 without an increment of NO release by ezetimibe led us to think that the reduction of this miR is not necessarily the only mechanism modulating the NO pathway.…”

“…On the other hand, ezetimibe also reduces cholesterol contents by interacting with the Niemann-Pick C1-like 1 (NPC1L1), which results in a decreased cholesterol absorption 8 . In addition, a number of pleiotropic effects have been described for statin therapy, including anti-inflammatory properties related to the vascular endothelium function 9 . Molecular mechanisms involved in statin-related anti-inflammatory effects and whether or not this depends on intracellular cholesterol reduction remains controversial.…”

Emerging Pharmacological Treatments to Prevent Abdominal Aortic Aneurysm Growth and Rupture

“…Numerous studies indicate hyperlipidemia as key factor in the development of AAA [10]; however, there is no clear evidence linking this relationship and recent data supports a contradictory view [7]. In spite of this, statins have been indicated as a potential tool to treat AAA based on its pleiotrophic effects on inflammation, oxidative stress and extracellular matrix composition, which causes reduction of AAA, independent of their cholesterol-lowering effect [11]. Steinmetz and coauthors showed that simvastatin suppresses the development of AAA induced by transient elastase perfusion of the abdominal aorta in both normal and hypercholesterolemic mice [12].…”

Beneficial Effects of Rosuvastatin in Heart of C57Bl/6 Mice with Diet- Induced Metabolic Syndrome - A Preliminary Study

“…In the control group and high fat groups treated with rosuvastatin, we observed lower levels of UCP2, which showed a lower activation of UCP2. This fact can be explained by the antioxidant properties of the statins and its induction power of mitochondrial biogenesis [13,21,[42][43][44].…”

“…These results are accounted for decrease in serum cholesterol levels as well as the pleiotropic effects, a fact that has drawn the attention of the medical community [19][20][21].…”