Abstract 1369: A New Murine Model of Diabetic Cardiomyopathy: The Female Leptin-Deficient, Black and Tan Brachyuric Mouse
Objective: Patients with diabetes have a 2-fold increased risk for congestive heart failure (CHF) and non-ischemic cardiomyopathy. Identifying mechanisms underlying diabetic cardiomyopathy would be facilitated greatly by the availability of a murine model replicating key disease features of cardiac hypertrophy, fibrosis and ventricular dysfunction.
Methods: To validate the leptin-deficient (ob/ob) black and tan brachyuric (BTBR) strain as a diabetic cardiomyopathy model, we compared plasma glucose levels, body weights, heart weights and myocardial fibrosis (by picrosirius red stain) in 22-week old BTBR ob/ob female mice and their wild-type controls (BTBR WT), as well as in two commonly-studied models of diabetic cardiomyopathy, C57BL/6J (B6) ob/ob mice and leptin receptor-deficient (db/db) Kaliss (KS) mice and their respective controls (B6 WT and KS db/+). BTBR ob/ob and WT mice also were studied at ages 8 and 16 weeks. Echocardiography was performed at 16 weeks in BTBR ob/ob and WT mice.
Results: As compared to their respective controls, body weights were increased similarly for BTBR ob/ob, B6 ob/ob and KS db/db mice at 22 weeks, though only BTBR ob/ob and KS db/db mice were hyperglycemic. However, as compared to their controls, only BTBR ob/ob mice had significantly greater heart weights (.19±.03 gm vs. .25±.03 gm, +32%, P<.0001) and fibrosis (.31±.11% vs. .60±.07%, +94%, P<.0001). At 16 weeks, BTBR ob/ob mice also had significantly greater heart weights (+31%, P<.0001) and fibrosis (+106%, P<.0001), with echocardiography confirming increased LV mass (+21%, P=.016) and a trend towards decreased diastolic function (P=.067).
Conclusions: In contrast to two commonly-studied mouse models of diabetic cardiomyopathy, BTBR ob/ob mice demonstrate significant cardiac hypertrophy and fibrosis. Thus, BTBR ob/ob mice may prove a useful tool for understanding the pathogenesis of this important complication of diabetes.