Simvastatin provides long ‐term improvement of left ventricular function and prevents cardiac fibrosis in muscular dystrophy

Duchenne muscular dystrophy (DMD), is the most common and severe neuromuscular disease affecting skeletal and cardiac muscle. Here, we showed that simvastatin both reversed pre ‐existing cardiac dysfunction and prevented its development during long‐term treatment of dystrophic mice. Simvastatin also prevented the progression of dystrophic cardiac fibrosis. Together, these findings indicate that simvastatin markedly improves cardiac health and function in dystrophic mic e, and therefore may provide a novel approach for treating cardiomyopathy in DMD patients. AbstractDuchenne muscular dystrophy (DMD), caused by absence of the protein dystrophin, is a common, degenerative muscle disease affecting 1:5000 males worldwide. With recent advances in respiratory care, cardiac dysfunction now accounts for 50% of mortality in DMD. Recently, we demonstrated that simvastatin substantially improved skeletal muscle health and function inmdx (DMD) mice. Given the known cardiovascular benefits ascribed to statins, the aim of this study was to evaluate the efficacy of simvastatin on cardiac function inmdx mice. Remarkably, in 12 ‐month oldmdx mice, simvastatin reversed diastolic dysfunction to normal after short ‐term treatment (8 weeks), as measured by echocardiography in animals anesthetized with isoflurane and administered dobutamine to maintain a physiological heart rate. This improvement in diastolic function was accompanied by increased phospholamban phosphorylation in simvastat...
Source: Physiological Reports - Category: Physiology Authors: Tags: Original Research Source Type: research