Abstract 659: Curcumin Ameliorates Cardiac Dysfunction in the Ovariectomized Diabetic mRen2.Lewis Rat by Inhibiting Renin Angiotensin System
Diabetes is a well-recognized independent risk factor for the development of cardiovascular disease in women. Moreover, hypertension and loss of estrogen are additional complicating factors to diabetic heart disease. Curcumin, an active compound in the widely used spice turmeric, exerts therapeutic potential in diabetes mellitus; however, the underlying mechanisms are not fully understood. The present study was designed to investigate the potential of curcumin to ameliorate early cardiac dysfunction in insulin- and estrogen-depleted hypertensive mRen2.Lewis rats by altering the renin angiotensin system as one of the major contributors to the development of diabetic cardiomyopathy. Ovariectomy (OVX) was performed at 10 weeks of age and diabetes (D) subsequently induced at 11 weeks with streptozotocin (65 mg/kg). Only animals that showed hyperglycemia greater than 200 mg/dl were considered diabetic. OVX-D rats were given curcumin at a dose of 200 mg/kg/day (OVX-D & CUR; n=7) or vehicle (OVX-D & VEH; n=8) by gastric gavage starting two days after streptozotocin injection. Intact non-diabetic mRen2.Lewis rats served as controls (C; n=9). After four weeks, concomitant insulin and estrogen depletion induced systolic and diastolic dysfunction, indicated by decreased fractional shortening (FS; C: 60.0 ± 1.5 vs OVX-D & VEH: 43.7 ± 2.2 %; p<0.05) and Tissue Doppler velocity at the level of mitral annulus (e’; C: 75.0 ± 3.4 vs OVX-D & VEH: 58.6 ± 5.6 mm/s; p<0.05) that was associated with increased blood pressure (BP; C: 131 ± 3 vs 179 ± 2 mmHg; p<0.05), elevated plasma angiotensin II (Ang II; C: 20 ± 4 vs 32 ± 2 pg/ml; p<0.05), and cardiac expression of Ang II type 1 receptor (AT1; C: 100 ± 12 vs 206 ± 33 %; p<0.05). Curcumin treatment did not affect BP (164 ± 6 mmHg; p>0.05) but attenuated cardiac systolic (FS: 53 ± 3%, p<0.05) and diastolic dysfunction (e’: 74 ± 3 mm/s; p<0.05) while reducing AT1 expression (120 ± 12 %; p<0.05) in the diabetic heart. It also decreased plasma Ang II to the levels not different from the controls (21.6 ± 3 pg/ml; p>0.05). In conclusion, the present study suggests that curcumin treatment, in a blood pressure independent manner, may ameliorate early cardiac dysfunction in estrogen- and insulin-depleted mRen2.Lewis rats by reducing Ang II signaling pathway.
Author Disclosures: J.L. VonCannon: None. Y. Jiao: None. D. Kim-Shapiro: None. J. Varagic: None.
- © 2014 by American Heart Association, Inc.