Simvastatin inhibits sPLA2 IIa expression in aorta and myocardium

Arch Med Res. 2009 Feb;40(2):67-72. doi: 10.1016/j.arcmed.2008.12.006.

Abstract

Background and aims: Group IIa secretory phospholipase A2 (sPLA2 IIa) induces atherosclerosis by altering systemic lipoprotein mechanism. The aim of this study was to investigate the expression and localization of sPLA2 IIa in atherosclerosis of rat aorta, myocardium and visceral adipose tissue (VAT) and to explore the effect of simvastatin on sPLA2 IIa expression.

Methods: Thirty male Wistar rats were randomly divided into three groups: control group, test group, and simvastatin group. Control group rats were fed with standard chow, whereas those in the test group were fed with a high cholesterol diet. Simvastatin (5 mg/kg/day per gavage) was given to the rats in simvastatin group in addition to the high cholesterol diet. At the end of 8 weeks, rats were sacrificed and sPLA2 IIa measured by immunocytochemistry.

Results: sPLA2 IIa was present in smooth muscle cells, aortic plaques, and also in myocardium and VAT. In addition, sPLA2 IIa expression in myocardium and aorta was much higher in the test group than in control group (p <0.01). However, expression of the enzyme in myocardium and aorta was significantly decreased in the simvastatin group compared to the test group (p <0.05). Immunostaining of sPLA2 IIa was also present in VAT, but no significant changes were found in levels of this enzyme among the three groups (p >0.05).

Conclusions: Myocardium and VAT may be two other important sources of sPLA2 IIa. Our data support the hypothesis that sPLA2 IIa may play a significant role in the pathogenesis of atherosclerosis. Simvastatin may reduce the process of atherosclerosis by decreasing the expression level of sPLA2 IIa in myocardium and aorta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / pharmacology*
  • Aorta / drug effects
  • Aorta / enzymology*
  • Aorta / pathology
  • Atherosclerosis / enzymology*
  • Atherosclerosis / pathology
  • Cholesterol / blood
  • Gene Expression
  • Group II Phospholipases A2 / antagonists & inhibitors*
  • Group II Phospholipases A2 / metabolism
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / enzymology
  • Intra-Abdominal Fat / pathology
  • Male
  • Myocardium / enzymology*
  • Myocardium / pathology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Rats
  • Rats, Wistar
  • Simvastatin / administration & dosage
  • Simvastatin / pharmacology*
  • Triglycerides / blood

Substances

  • Anticholesteremic Agents
  • Triglycerides
  • Cholesterol
  • Simvastatin
  • Group II Phospholipases A2