Abstract 201: Enhancing Pgc-1α Activity Improves Heart Function Through Activating Mitochondrial Biogenesis in Chagas Disease

• DOI: 10.1161/res.117.suppl_1.201
• Publication Date: 2021-07-03T09:14:18Z
• Authors: Xianxiu Wan; Jianjun Wen; Koo Sue-jie
• Keywords: TFAM; NRF1; PPARGC1A; Sirtuin 1

Chronic chagasic cardiomyopathy (CCM) is presented with ventricular hypertrophy and contractile dysfunction that can lead to heart failure. I have found a substantial decline in mitochondrial biogenesis SIRT1/PGC-1α activity ensue chronic mice. It was evidenced by the DNA content as well mRNA levels of encoded genes mtDNA replication machinery. Further, SIRT1 (required for PGC-1α activation) decreased associated nuclear PGC-1-regulated NRF1 transcription factor hearts. The size number were also reduced heart, determined electron microscopy. Therefore, we hypothesized enhancing agonist would improve function through activating Chagasic disease. Mice infected T. cruzi, beginning at day 90 post-infection (pi), treated resveratrol (SIRT1 agonist) or metformin (AMPK agonist, enhance activity) 21 days; then monitored 150 days pi. We treatment partially attenuated (stroke volume, cardiac output, ejection fraction, rate) These benefits improved expression though involved not improved. Treatment significantly beneficial improving CCM outcomes. partial effects could be due inefficient activation delayed start treatment. plan treat mice SIRT1720 (10 fold more active than resveratrol) during indeterminate phase cruzi infection next set experiments. This study will our understanding molecular immune mechanisms disease provide novel chronically-infected patients.