The role of HMG-CoA reductase inhibition in endothelial dysfunction and inflammation

Paolo Gelosa, Mauro Cimino, Alice Pignieri, Elena Tremoli, Uliano Guerrini, Luigi Sironi

Research output: Contribution to journalArticlepeer-review

Abstract

Statin-induced inhibition of HMG-CoA reductase reduces cholesterol production and prevents the formation of many non-steroidal isoprenoid compounds, such as farnesylpyrophosphate and geranylgeranylpyrophosphate, that act as lipid attachments for the post-translational modification of various proteins, including the G-proteins and transcription factors involved in a number of cell processes. However, the blockade of isoprenylation elicited by statin treatment also has biological effects on cell function that go beyond the decrease in cholesterol synthesis: these are the so-called "pleiotropic" effects that mainly relate to vascular function. Endothelial dysfunction is an independent predictor of cardiovascular events that correlates with inflammation markers/mediators and robust predictors of cardiovascular diseases such as increased high-sensitivity C-reactive protein levels. The results of in vivo and in vitro studies indicate that the statins have beneficial effects unrelated to cholesterol lowering, such as improving endothelial function, increasing myocardial perfusion, and enhancing the availability of nitric oxide. This review describes the pleiotropic effects of statins that may be involved in modulating/preventing endothelial dysfunction and inflammatory processes, as well as the cellular and molecular mechanisms through which they improve endothelial function.

Original languageEnglish
Pages (from-to)567-577
Number of pages11
JournalVascular Health and Risk Management
Volume3
Issue number5
Publication statusPublished - 2007

Keywords

  • Endothelial dysfunction
  • HMG-CoA reductase
  • Inflammation
  • Nitric oxide
  • Statins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hematology
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health

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