Effect of atorvastatin (Lipitor) on myocardial apoptosis and caspase-8 activation following coronary microembolization

Cell Biochem Biophys. 2011 Nov;61(2):399-406. doi: 10.1007/s12013-011-9199-z.

Abstract

We determined the effect of atorvastatin on myocardial apoptosis and caspase-8 activation following coronary microembolization (CME) in a rat model. For this, 50 rats were randomly and equally divided into CME; sham-operated (control); atorvastatin lavage; gastric lavage control; and caspase-8 inhibitor (CHO) groups. In CME animals, a microembolization ball was injected through the left ventricle. Sham animals were injected with normal saline (NS). Atorvastatin group received atorvastatin gastric lavage once-a-day, 1 week before surgery. Gastric lavage controls had similar lavage with NS. CHO group was i.p-injected (CHO: 10 mg/kg) 30 min before surgery. Cardiac indices in each group were determined by echocardiography 6-h postoperatively. TUNEL assay and western blot were used for myocardial apoptosis and expression of caspases-3/-8, respectively. Echocardiography data show that left ventricular ejection fraction (LVEF) in CME group was significantly decreased (P < 0.05) compared with sham controls. Besides, left ventricular fractional shortening (FS) and cardiac output (CO) were also decreased with an increase in left ventricular end-diastolic dimension (LVEDd). Atorvastatin and CHO animals had significantly improved (P < 0.05) cardiac function compared with CME group. Myocardial apoptosis and activation levels of caspases-3/-8 were significantly increased (P < 0.05) compared with sham; myocardial apoptosis and activation levels of caspases-3/-8 were significantly decreased (P < 0.05) in atorvastatin and CHO groups compared with CME group. In conclusion, atorvastatin pretreatment suppressed post-CME myocardial apoptosis and improved cardiac function through the blockade of a myocardial death receptor-mediated apoptotic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Atorvastatin
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism*
  • Coronary Vessels / drug effects*
  • Embolization, Therapeutic*
  • Enzyme Activation / drug effects
  • Heart / drug effects
  • Heart / physiology
  • Heptanoic Acids / pharmacology*
  • Male
  • Myocardium / cytology*
  • Myocardium / metabolism*
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Death Domain / metabolism

Substances

  • Heptanoic Acids
  • Pyrroles
  • Receptors, Death Domain
  • Atorvastatin
  • Caspase 3
  • Caspase 8