O15 DIFFERENTIAL CARDIAC MACROPHAGE POLARIZATION IS ASSOCIATED WITH BETTER PRECLINICAL MARKERS IN FEMALE SEX VERSUS MALE SEX WITH HYPERTENSION AND METABOLIC SYNDROME

Abstract

Background: Women compared to men with hypertension (HT) and metabolic syndrome (MS) exhibit better clinical outcomes. In the preclinical model of HT-MS, female mice develop attenuated cardiac remodeling (CRM) compared to male mice (not mediated by sex hormones). Male cardiac macrophages (Mo) from mice are more susceptible to inflammatory stimuli. It is unknown whether subpopulations of cardiac pro-inflammatory Mo and resident repair Mo differ between males and females. Purpose: To characterize, in male and female mice with HT-MS, the cardiac pro-inflammatory cardiac Mo derived from monocytes (CCR2+MHCII+) and the resident repair Mo (CCR2-MHCII+ and CCR2- MHCII-). Methods: 12-week-old male and female C57BL/6N mice were assigned to experimental groups: high-fat diet + L-NAME or control diet. Body weight (BW), systolic (SBP) and diastolic (DBP) blood pressure, glucose and exercise tolerance, cardiac function and cardiac Mo CCR2+MHCII+, CCR2-MHCII+, CCR2- MHCII- were determined. Results: (mean ± SEM, n=11-18 mice/group). Compared with males, females with HT-MS gained less BW (14% vs. 22%, p<0.05), 2), had lower glucose levels (265±13 mg/dL vs 191±14 vs., p<0.001) and covered a greater distance on the treadmill (p<0.05). SBP and DBP was similary increased vs. their controls in both groups. In males but not in females with HT-MS both the LV septum and posterior wall were thicker vs controls (p< 0.001). Left atrium size increased 7.6% in females and 20% in males. In the myocardium, CR2+MHCII+ Mo increased by 58% only in males (p<0.001, F=11.7). The CCR2-MHCII- Mo increased by 75% in HT-MS females vs their controls, (p<0.001,F=18.7) and vs males. The CCR2-MHCII+ Mo decreased by 28.4% only in males (p<0.05, F=3.7). Conclusion: In females with HT-MS protective resident cardiac Mo increased significantly which was associated to less CRM and better exercise performance. Activation of resident cardiac Mo may be an important mechanism for prevention and treatment of CRM by HT and MS.