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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

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

Sarcoplasmic Reticulum Calcium-Transporting ATPases

drug effects

metabolism

Sulfonamides

pharmacology

Ventricular Remodeling

drug effects

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)