Frontiers in Pharmacology (Jul 2022)
QiShenYiQi Pill Ameliorates Cardiac Fibrosis After Pressure Overload-Induced Cardiac Hypertrophy by Regulating FHL2 and the Macrophage RP S19/TGF-β1 Signaling Pathway
- Gulinigaer Anwaier,
- Gulinigaer Anwaier,
- Gulinigaer Anwaier,
- Gulinigaer Anwaier,
- Gulinigaer Anwaier,
- Gulinigaer Anwaier,
- Gulinigaer Anwaier,
- Ting-Ting Xie,
- Ting-Ting Xie,
- Ting-Ting Xie,
- Ting-Ting Xie,
- Ting-Ting Xie,
- Ting-Ting Xie,
- Ting-Ting Xie,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Chun-Shui Pan,
- Chun-Shui Pan,
- An-Qing Li,
- An-Qing Li,
- An-Qing Li,
- An-Qing Li,
- An-Qing Li,
- An-Qing Li,
- An-Qing Li,
- Li Yan,
- Li Yan,
- Li Yan,
- Li Yan,
- Li Yan,
- Li Yan,
- Di Wang,
- Di Wang,
- Di Wang,
- Di Wang,
- Di Wang,
- Di Wang,
- Di Wang,
- Fan-Kai Chen,
- Fan-Kai Chen,
- Fan-Kai Chen,
- Fan-Kai Chen,
- Fan-Kai Chen,
- Fan-Kai Chen,
- Fan-Kai Chen,
- Ding-Zhou Weng,
- Ding-Zhou Weng,
- Ding-Zhou Weng,
- Ding-Zhou Weng,
- Ding-Zhou Weng,
- Ding-Zhou Weng,
- Ding-Zhou Weng,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Kai Sun,
- Xin Chang,
- Xin Chang,
- Xin Chang,
- Xin Chang,
- Xin Chang,
- Xin Chang,
- Xin Chang,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Yu Fan,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jing-Yan Han,
- Jian Liu,
- Jian Liu,
- Jian Liu,
- Jian Liu,
- Jian Liu,
- Jian Liu
Affiliations
- Gulinigaer Anwaier
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Gulinigaer Anwaier
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Gulinigaer Anwaier
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Gulinigaer Anwaier
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Gulinigaer Anwaier
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Gulinigaer Anwaier
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Gulinigaer Anwaier
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Ting-Ting Xie
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Ting-Ting Xie
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Ting-Ting Xie
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Ting-Ting Xie
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Ting-Ting Xie
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Ting-Ting Xie
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Ting-Ting Xie
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Chun-Shui Pan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Chun-Shui Pan
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Chun-Shui Pan
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Chun-Shui Pan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Chun-Shui Pan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Chun-Shui Pan
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- An-Qing Li
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- An-Qing Li
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- An-Qing Li
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- An-Qing Li
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- An-Qing Li
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- An-Qing Li
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- An-Qing Li
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Li Yan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Li Yan
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Li Yan
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Li Yan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Li Yan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Li Yan
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Di Wang
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Di Wang
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Di Wang
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Di Wang
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Di Wang
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Di Wang
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Di Wang
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Fan-Kai Chen
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Fan-Kai Chen
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Fan-Kai Chen
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Fan-Kai Chen
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Fan-Kai Chen
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Fan-Kai Chen
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Fan-Kai Chen
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Ding-Zhou Weng
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Ding-Zhou Weng
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Ding-Zhou Weng
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Ding-Zhou Weng
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Ding-Zhou Weng
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Ding-Zhou Weng
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Ding-Zhou Weng
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Kai Sun
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Kai Sun
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Kai Sun
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Kai Sun
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Kai Sun
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Kai Sun
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Xin Chang
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Xin Chang
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Xin Chang
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Xin Chang
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Xin Chang
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Xin Chang
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Xin Chang
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Jing-Yu Fan
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jing-Yu Fan
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Jing-Yu Fan
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jing-Yu Fan
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jing-Yu Fan
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Jing-Yu Fan
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Jing-Yan Han
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Jing-Yan Han
- Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China
- Jing-Yan Han
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Jing-Yan Han
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jing-Yan Han
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jing-Yan Han
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Jing-Yan Han
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- Jian Liu
- Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China
- Jian Liu
- Academy of Integration of Chinese and Western Medicine, Peking University Health Science Center, Beijing, China
- Jian Liu
- Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jian Liu
- Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People’s Republic of China, Beijing, China
- Jian Liu
- State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tianjin, China
- Jian Liu
- Beijing Microvascular Institute of Integration of Chinese and Western Medicine, Beijing, China
- DOI
- https://doi.org/10.3389/fphar.2022.918335
- Journal volume & issue
-
Vol. 13
Abstract
Purpose: Heart failure (HF) is a leading cause of morbidity and mortality worldwide, and it is characterized by cardiac hypertrophy and fibrosis. However, effective treatments are not available to block cardiac fibrosis after cardiac hypertrophy. The QiShenYiQi pill (QSYQ) is an effective treatment for chronic HF. However, the underlying mechanism remains unclear.Methods: In the present study, a pressure overload-induced cardiac hypertrophy model was established in rats by inducing ascending aortic stenosis for 4 weeks. QSYQ was administered for 6 weeks, and its effects on cardiac fibrosis, myocardial apoptosis, RP S19 release, macrophage polarization, TGF-β1 production, and TGF-β1/Smad signaling were analyzed. In vitro studies using H9C2, Raw264.7, and RDF cell models were performed to confirm the in vivo study findings and evaluate the contribution to the observed effects of the main ingredients of QSYQ, namely, astragaloside IV, notoginsenoside R1, 3,4-dihydroxyl-phenyl lactic acid, and Dalbergia odorifera T. C. Chen oil. The role of four-and-a-half LIM domains protein 2 (FHL2) in cardiac fibrosis and QSYQ’s effects were assessed by small interfering RNAs (siRNAs).Results: QSYQ ameliorated cardiac fibrosis after pressure overload-induced cardiac hypertrophy and attenuated cardiomyocyte apoptosis, low FHL2 expression, and TGF-β1 release by the injured myocardium. QSYQ also inhibited the following: release of RP S19 from the injured myocardium, activation of C5a receptors in monocytes, polarization of macrophages, and release of TGF-β1. Moreover, QSYQ downregulated TGF-βR-II expression induced by TGF-β1 in fibroblasts and inhibited Smad protein activation and collagen release and deposition.Conclusion: The results showed that QSYQ inhibited myocardial fibrosis after pressure overload, which was mediated by RP S19-TGF-β1 signaling and decreased FHL2, thus providing support for QSYQ as a promising therapy for blocking myocardial fibrosis.
Keywords
