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Current Atherosclerosis Reports

, Volume 14, Issue 2, pp 135–139 | Cite as

Pleiotropic Effects of Statins: The Role of Eicosanoid Production

  • Yochai Birnbaum
  • Yumei Ye
Coronary Heart Disease (J Farmer, Section Editor)

Abstract

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have potent anti-inflammatory, vasodilatory and anti-platelet effects that are independent of the lipid-lowering effects. These non–lipid-lowering or pleiotropic effects are dependent on HMG-CoA reductase inhibition in tissues other than the liver. In animal models, high-dose statins upregulate cytosolic phospholipase A2 and cyclooxygenase-2, leading to increased production of prostacyclin and 15-deoxy-PGJ2. In addition, statins activate protein kinase A, which phosphorylates 5-lipoxygenase, resulting in decreased production of the pro-inflammatory leukotrienes and increased production of 15-epi-lipoxin A4, an eicosanoid with potent anti-inflammatory and inflammation-resolution properties. It is unclear, however, whether these effects occur in the clinical setting and whether these effects (partially) explain the anti-inflammatory effects of statins in patients.

Keywords

Arachidonic acid Aspirin LDL cholesterol Cyclooxygenase-2 Eicosanoids Inflammation 5-lipooxygenase Pleiotropic effects Prostacyclin Protein kinase A (PKA) Statins 

Notes

Disclosure

Y. Birnbaum has received grants (payable to his institution) from Pfizer, Takeda, Merck, and AstraZeneca; has received consulting fees from Takeda; and has had travel expenses for meetings covered by Takeda and Merck. Y. Ye has received grants (payable to his institution) from Pfizer, Takeda, Merck, and AstraZeneca; has received consulting fees from Takeda; and has had travel expenses for meetings covered by Takeda and Merck.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.John S. Dunn Chair in Cardiology Research and Education, The Department of Medicine, Section of CardiologyBaylor College of MedicineHoustonUSA
  2. 2.The Department of Biochemistry and Molecular BiologyUniversity of Texas Medical BranchGalvestonUSA
  3. 3.Texas Heart InstituteSt Luke’s Episcopal HospitalHoustonUSA
  4. 4.The Department of Biochemistry and Molecular BiologyUniversity of Texas Medical BranchGalvestonUSA

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