O17 THE PROGRESSION OF HYPERTENSION WITH OBESITY AND DIABETES FAVORS CARDIAC PRO-INFLAMMATORY MACROPHAGES AND DIASTOLIC DYSFUNCTION

Abstract

Background: In most patients, hypertension (HT) is accompanied by obesity and diabetes. Cell-specific mechanisms like accumulation of macrophages, and dysregulation of innate immune pathways play important roles in cardiac remodeling (CR). Macrophages (Mo) exhibit phenotypic heterogeneity in response to tissue micro-environment. It is unknown whether in the heart the subpopulations of pro-inflammatory Mo (CCR2+MHCII+) and resident repair Mo (CCR2-MHCII+ and CCR2-MHCII-) differ in the development of the chronic HT, obesity and diabetes. Objective. To determine in male with HT and or obesity and diabetes, the pro-inflammatory cardiac Mo derived from monocytes (CCR2+MHCII+) and the resident repair Mo (CCR2-MHCII+ and CCR2- MHCII-). Methods: 12-week-old male C57BL/6N mice were assigned to experimental groups: control diet, high-fat diet (HFD, 60% kcal from fat), L-NAME (L,0.65 g/L in drinking water) and HFD+L for 5 and 15 weeks. Body weight (BW), systolic (SBP) and diastolic blood pressure, glucose and exercise capacity (EC), cardiac function and cardiac Mo CCR2+MHCII+, CCR2-MHCII+, CCR2- MHCII- were determined. Results: (mean ± SEM, n=9-12). During 15 weeks, HFD and HFD+L groups showed significantly higher BW and glucose intolerance vs. control and L (p <0.001, F=28.4; p<0.001, F=10.3, respectively). EC as lower in the HFD and HFD+L groups compared to control and L (p<0.059). Echocardiographic parameters showed a significant increase in the size of the left atrium (p<0.001, F=38.9) and diastolic dysfunction in the HFD+L group vs control, HFD and L (p<0.001, F=35.6). No changes in ejection fraction and shortening fraction. The thickness of the septal wall and posterior wall was significantly greater in the HFD+L and HFD groups (p<0.0001, F=10.6 and p<0.0001, F=14.6, respectively). The L hearts showed a significant increase in CCR2-MHCII- (p<0.0001, F=68.6) and a significant decrease in CCR2+ MHCII+ (p<0.001, F=13.7), compared to the control and HFD groups. Conclusion: The progression of HT with obesity and diabetes favors cardiac pro-inflammatory macrophages and diastolic dysfunction.