Rong-Rong Gao1, Xiao-Dong Wu1, Hui-Min Jiang2, Yu-Jiao Zhu3, Yan-Li Zhou1, Hai-Feng Zhang1, Wen-Ming Yao1, Yong-Qin Li3, Xin-Li Li1. 1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. 2. Clinical Laboratory Center, Beijing Hospital of Traditional Chinese Medicine, Beijing 100010, China. 3. Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai 200444, China.
Abstract
BACKGROUND: Clinical study has demonstrated that the traditional Chinese medicine Qiliqiangxin (QLQX) has protective effects on heart failure. Phenylephrine (PE) is an important inducing factor for cardiac hypertrophy and our previous studies have showed that QLQX attenuates PE-induced cardiac hypertrophy. Besides, QLQX protects against cardiac remodeling after myocardial infarction via activating PPARγ. However, whether QLQX prevents PE-induced cardiac hypertrophy through PPARγ and its coactivator PGC-1α is still unknown. METHODS: The effects of QLQX were investigated based on PE induced cardiac hypertrophy mouse models. Echocardiography and hematoxylin-eosin (HE) staining were used to determine cardiac function and cross-sectional area, respectively. Quantitative real time PCR (qRT-PCR) was used to determine ANP and BNP expressions. Based on primary neonatal rat ventricular cardiomyocytes (NRVMs) treated with PE, the cell size and expressions of ANP and BNP were determined by immunofluorescent staining and qRT-PCR, respectively. In addition, western blot was used to determine PPARγ and PGC-1α expressions. RESULTS: In present study, we confirmed that QLQX could significantly attenuate cardiac hypertrophy in mice treated with PE. Then we showed that PPARγ and PGC-1α were downregulated in PE-induced cardiac hypertrophy, and QLQX could block the decrease of PPARγ and PGC-1α both in vitro and in vivo. Importantly, we found that PPARγ inhibitors or PGC-1α siRNAs eliminated the protective effects of QLQX on PE-induced cardiac hypertrophy. CONCLUSIONS: Our study suggested that QLQX prevents from PE-induced cardiac hypertrophy by activating PPARγ and its coactivator PGC-1α.
BACKGROUND: Clinical study has demonstrated that the traditional Chinese medicine Qiliqiangxin (QLQX) has protective effects on heart failure. Phenylephrine (PE) is an important inducing factor for cardiac hypertrophy and our previous studies have showed that QLQX attenuates PE-induced cardiac hypertrophy. Besides, QLQX protects against cardiac remodeling after myocardial infarction via activating PPARγ. However, whether QLQX prevents PE-induced cardiac hypertrophy through PPARγ and its coactivator PGC-1α is still unknown. METHODS: The effects of QLQX were investigated based on PE induced cardiac hypertrophy mouse models. Echocardiography and hematoxylin-eosin (HE) staining were used to determine cardiac function and cross-sectional area, respectively. Quantitative real time PCR (qRT-PCR) was used to determine ANP and BNP expressions. Based on primary neonatal rat ventricular cardiomyocytes (NRVMs) treated with PE, the cell size and expressions of ANP and BNP were determined by immunofluorescent staining and qRT-PCR, respectively. In addition, western blot was used to determine PPARγ and PGC-1α expressions. RESULTS: In present study, we confirmed that QLQX could significantly attenuate cardiac hypertrophy in mice treated with PE. Then we showed that PPARγ and PGC-1α were downregulated in PE-induced cardiac hypertrophy, and QLQX could block the decrease of PPARγ and PGC-1α both in vitro and in vivo. Importantly, we found that PPARγ inhibitors or PGC-1α siRNAs eliminated the protective effects of QLQX on PE-induced cardiac hypertrophy. CONCLUSIONS: Our study suggested that QLQX prevents from PE-induced cardiac hypertrophy by activating PPARγ and its coactivator PGC-1α.
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