Abstract P3113: Apyrase But Not Dipyridamole Improves Cardiac Function In Ovariectomized High-fat Diet Mice

Abstract

Objectives: Postmenopausal women with metabolic disease are predisposed to develop cardiovascular disease. Our previous experiments have shown that these women experience purinergic/adenosinergic signaling alteration resulting in diastolic dysfunction. We hypothesize that these signaling alterations are reversible and to demonstrate we used exogenous CD39 agonist (apyrase) and an ENT-1 inhibitor (dipyridamole), in a murine model simulating postmenopausal women. Methods: We fed 23 C57BL/6 female mice a HFD (40% kcal) from 5 weeks of age and performed ovariectomy at 12 weeks. Intraperitoneal (IP) injections were given daily to three groups for 10 days at 28 weeks. The following groups and dosages were used: apyrase (9 mice, 200U/kg), dipyridamole (9 mice, 20mg/kg), and saline (5 mice). At 30 weeks, mice were assessed with an EchoMRI for body composition, and transthoracic echocardiography (TTE) used for evaluation of cardiac function while mice were anesthetized with 2.5% isoflurane. Results: Our apyrase-treated mice, had significantly lowered values in E/E’, E/A, with increased Ejection Fraction and Fraction Shortening when compared to the saline treated groups, analyzed with t-test. Apyrase also had lower body weight, lean mass, fat mass, and heart/body weight percentage, when compared to saline (p<0.05). Dipyridamole had significant increase in LV diastolic volume and IVRT when compared to our saline group. Conclusion: Our findings could suggest that increased ectonucleotidase activity may ameliorate diastolic dysfunction experienced in our murine model. Future studies are needed to confirm its effect in postmenopausal women.