Beneficial effect of rosuvastatin on cardiac dysfunction is associated with alterations in calcium-regulatory proteins.

Abstract

AIMS:

The normal expression of Ca(2+)-regulatory protein is critical for efficient myocardial function. The present study tested the hypothesis that rosuvastatin treatment may attenuate left ventricular (LV) remodelling and dysfunction in the failing heart, which may be associated with alterations of Ca(2+)-regulatory protein.

METHODS AND RESULTS:

We investigated the change of LV remodelling and function in a rat model of cardiac dysfunction due to myocardial infarction (MI) with or without rosuvastatin (10 mg/kg/day) treatment for 10 weeks. The protein expression of sarcoplasmic reticulum Ca(2+) ATPase (SERCA)2a, phospholamban (PLB), and phospho-PLB at serine-16 (pSer16-PLB), as well as SERCA activity, interleukin (IL)-6, and IL-10 levels were evaluated. After rosuvastatin treatment, LV remodelling and dysfunction were prevented. Rosuvastatin prevented the decrease of SERCA2a and pSer16-PLB expression, increased SERCA activity, but showed no effect on PLB expression. Furthermore, rosuvastatin reduced the increased IL-6 level and further elevated IL-10 level in the peri-infarct and remote zones of MI. Serum lipid levels remained unchanged.

CONCLUSION:

Rosuvastatin is effective in preventing LV remodelling and dysfunction in the failing heart. The molecular mechanism may be related to normalization of SERCA2a expression, SERCA activity, and pSer16-PLB levels, as well as through cytokine alterations independent of its lipid-lowering effect.

• Authors: Ying Yang, Yun Mou, Shen-Jiang Hu, Michael Fu
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 11 Issue 1 Pg. 6-13 (Jan 2009) ISSN: 1388-9842 [Print] England
• PMID: 19147451 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• Fluorobenzenes
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Interleukin-6
• Pyrimidines
• Sulfonamides
• phospholamban
• Interleukin-10
• Rosuvastatin Calcium
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• Atp2a2 protein, mouse

Topics

• Animals
• Calcium-Binding Proteins (drug effects, metabolism)
• Disease Models, Animal
• Fluorobenzenes (pharmacology)
• Heart (physiopathology)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Interleukin-10 (blood)
• Interleukin-6 (blood)
• Male
• Organ Size (drug effects)
• Pyrimidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Rosuvastatin Calcium
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (drug effects, metabolism)
• Sulfonamides (pharmacology)
• Ventricular Remodeling (drug effects)