Abstract 10928: Chlorogenic Acid Ameliorates Pressure Overload-Induced Cardiac Hypertrophy in Mouse Models

Abstract

Introduction: Cardiac hypertrophy leading to heart failure is one of the critical causes of morbidity and mortality. Although social interest in treatment and prevention of cardiovascular disease is high, sufficient outcome has not been obtained yet. Chlorogenic acid (CGA) is one of the most abundant phenolics in plants, and is called caffeic acid. Recently, the cardioprotective effects of CGA which ameliorate isoproterenol-induced hypertrophy in vitro research have been reported. However, it has not been elucidated whether CGA affects cardiac hypertrophy in vivo models with TAC. Hypothesis: We assessed the hypothesis that the administration of CGA has protective effect on TAC-induced cardiac hypertrophy. Methods: We used mouse models of cardiac hypertrophy induced by TAC for four weeks. Mice were randomly assigned to sham, TAC, and TAC+CGA groups. CGA was administered at dose of 40mg/kg intraperitoneally once a day for four weeks after the TAC operation. cardioprotective effect was investigated by echocardiography and histological analysises. In addition, immunoblot and metabolome analysises and biomedical assays were conducted in excised hearts. Statistical analysis was performed by one-way ANOVA. All data are expressed as mean ± SD. Statistical significance was defined as P < 0.05. Results: We evaluated sham group (n=8), TAC group (n=7), TAC+CGA group (n=7) four weeks after TAC operation. TAC group showed an increase of heart weight, which was attenuated by CGA (120.3±9.3mg, 148.8±9.0mg, 126.6±6.2mg, p<0.05). Consistently, echocardiography revealed that the change of myocardial diastolic wall thickness (0.79±0.1mm, 1.13±0.1mm, 0.93±0.1mm, p<0.05). Histological analysis indicated that fibrosis induced by TAC was alleviated by CGA. According to immunoblot analysis, TAC group showed overexpression of TGF-β, IL-6, and TNF-α. In addition, the enhancements of glycolysis and TCA cycle were indicated in metabolome analysis. These changes were modulated by CGA administration. Conclusion: In conclusion, the present study revealed that CGA administration ameliorates pressure overload-induced cardiac hypertrophy in rodent model. As a key factor, expression of inflammatory cytokines and modulation of glucose metabolism were observed.