Role of Prostaglandin D Synthase in Cardiac Remodeling Secondary to Pressure Overload in Rats

Abstract

We sought to compare the effects of specific COX 2 inhibitors (Nimesulide) or Prostaglandin D synthase inhibitor (HQL 79) on cardiac remodeling secondary to pressure overload in rats. In vivo left ventricular (LV) structure and function was assessed by pressure/volume catheter at 28 days post surgery in six groups (n ≥ 6 per group): sham‐operated (Sham); untreated pressure overload (PO); Prevention or intervention groups treated with either NIMEsulide (25 mg/kg/d) or HQL 79 (10 mg/kg/d). The prevention strategy was initiated prior to induction of pressure overload and continued to day 14. Intervention treatment strategy started on day 14 post induction of pressure overload and continued till day 28. Both prevention and intervention NIME treatments attenuated the PO induced change in LV mass. Prevention treatment with HQL 79 attenuated this change. End diastolic volume was significantly decreased (by 29%) in PO group compared to Sham. Both treatment strategies with HQL 79 significantly attenuate this change. Prevention treatment with Nimesulide significantly attenuated the change in PO induced increase in total collagen levels, whereas both prevention and intervention treatment with HQL 79 significantly attenuated fibrosis. These findings indicate that cardiac remodeling during pressure overload occurs by Prostaglandin D2 mediated inflammatory pathway and can be attenuated using PGD synthase inhibitors.