Duchenne muscular dystrophy (DMD) is a severe X-linked muscle disease caused by mutations in the dystrophin gene. We found that hematopoietic prostaglandin (PG) D synthase (HPGDS) was induced in damaged muscle fibers in DMD patient and model mice, mdx. We have shown that chronic treatment of HPGDS inhibitor in mdx mice prevent the DMD progression. On the other hand, cardiac failures are the most common causes of death in DMD patients. In this study, we investigate role of PGD2 to cardiac function and morphology in mdx mice.
Dilated cardiomyopathy was induced in mdx mice by thyroid hormone (T3)-treatment. T3 (2 mg/kg) was daily injected subcutaneously for 2-3 weeks. HPGDS inhibitor or D-type prostanoid receptor (DP-1) antagonist was daily administered in T3-treated mdx mice.
We detected fibrosis and cardiac inflammation in the heart in T3-treated mdx mice, but not in control mice treated with T3. mRNA of HPGDS, cyclooxygenase (COX)-1, and COX-2, DP-1 and also DP-2 were significantly upregulated. After HPGDS inhibitor or DP1 antagonist treatment in T3-treated in mdx, the hypertrophy of heart was significantly reduced compared to the vehicle-treated mdx mice. HPGDS inhibitor treatment lowered the serum cardiac troponin I, prevented the expression of periostin and improved deteriorated cardiac functions.