Abstract 4369459: Depressive symptoms have a differential expression in two models of heart failure

Introduction: Patients with HFpEF present a higher prevalence of major depressive disorder MDD (13%) than patients with HFrEF (6%). Several studies report that HFpEF and depression, share proinflammatory cytokines, including IL-33, which plasma concentration has a positive correlation with left ventricle diastolic disfunction and depressive symptoms. In addition, downregulation of the astrocyte derived IL-33 in the amygdala prevents the development of depression in mice. However, there is no explanation for this difference. Hypothesis: a mice model of HFpEF but not HFrEF, develops depression-like behavior and inflammation at the amygdala. Methodes: eight-week-old male C57BL/6 mice, randomly assigned to the following groups. HFpEF group: mice fed with ad libitum HFD (60% Fat) and drinking water with L-NAME (0.5g/L) for 12 weeks, HFrEF: mice implanted with a subcutaneous pump releasing 0.69 µg/kg/day angiotensin for 4 weeks and drinking water with L-NAME (0.1 g/l) + 1% NaCl, control: mice fed with ad libitum chow diet and tap water for 12 weeks. To determine cardiac hypertrophy and function, we employed echocardiographic imaging to assess relaxation time (IVRT) and deceleration time (DRT), E/A, fractional shortening (FS), ejection fraction (EF), and measured the left ventricle cardiomyocyte cross-sectional area. To diagnose depression, we employed the open field test (OF), sucrose preference (SP) and novelty suppressed feeding (NSF). To determine inflammation, we measured IL-33, IL-10, IL-6 and IL-1β and GFAP. For the statistical analysis we employ a one-way ANOVA followed by a Tukey test or a Kruskal-Wallis test based on the normality of the data calculated by the Kolmogorov-Smirnov test. Results: HFpEF presented a 26% increase in cardiomyocyte area, IVRT and DRT, with no significant differences in FS, or EF, an 1.3 fold change in E/A and a E/e >30, an increased expression of GFAP (1.7-fold), IL-1β (1.9-fold), and IL-33 (1.8-fold), and a 50% downregulation of IL-10 in the amygdala. HFrEF, showed a 200% increase in the cardiomyocyte area, as well as EF <50% and FS <30%, without changes in the E/A and E/e ratio and cytokine expression. In the behavioral tests, HFpEF exhibited a reduction of 11% in the SP, a latency of 53s (NSF), and expended 20% more time at the edges (OF), while HFrEF did not show differences. Conclusion: HFpEF, but not HFrEF, promotes cardiac hypertrophy and depression-like behavior accompanied by increased IL-33 expression in the amygdala.