2. Academic Validation
  3. Higenamine Improves Cardiac and Renal Fibrosis in Rats With Cardiorenal Syndrome via ASK1 Signaling Pathway

Higenamine Improves Cardiac and Renal Fibrosis in Rats With Cardiorenal Syndrome via ASK1 Signaling Pathway

  • J Cardiovasc Pharmacol. 2020 Jun;75(6):535-544. doi: 10.1097/FJC.0000000000000822.
Ting Deng 1 2 3 4,  Zhenming Wei 1 2 3,  Akindavyi Gael 1 2 3,  Xiaofang Deng 5,  Yunfeng Liu 1 2 3,  Jun Lai 1 2 3,  Liwei Hang 1 2 3,  Quanneng Yan 1 2 3,  Qiang Fu 1 2 3,  Zhiliang Li 1 2 3
Affiliations

Affiliations

  • 1 Department of Cardiology, Laboratory of Heart Center, Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Guangdong Provincial Biomedical Engineering Technology, Research Center for Cardiovascular Disease, Guangdong, China.
  • 3 Sino-Japanese Cooperation Platform for Translational Research in the Heart Failure, Guangzhou, China.
  • 4 Department of Cardiovascular Disease, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; and.
  • 5 Guangdong Provincial People's Hospital, Guangzhou, China.
PMID: 32168151 DOI: 10.1097/FJC.0000000000000822
Abstract

The pathogenesis of cardiorenal syndrome (CRS) is very complex, and currently there is no effective treatment for CRS. Higenamine (HI) has been shown to improve cardiac function in rats with heart failure. However, the role of higenamine in CRS remains unknown. Here, in vitro, higenamine treatment markedly reduced neonatal rat cardiac fibroblast collagen synthesis and inhibited neonatal rat cardiac myocyte hypertrophy. In our study, a rat model of type 2 CRS was induced by left anterior descending coronary artery ligation combined with 5/6 subtotal nephrectomy (STNx). Higenamine treatment decreased serum creatinine (Scr), blood urea nitrogen, and brain natriuretic peptide levels and was capable of improving left ventricular remodeling and systolic function in CRS rats, accompanied with decreased expression of transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA) and collagen I (Col1A1). Moreover, higenamine significantly inhibited the protein expression of phosphorylated Apoptosis signal-regulated kinase 1 (p-ASK1) and downstream mitogen-activated protein kinases (MAPK) (ERK, P38)/NF-κB in cardiorenal tissues of CRS rats and neonatal rat cardiac fibroblast/neonatal rat cardiac myocyte cells. Our study demonstrated that higenamine improved cardiorenal function in CRS rats and attenuated heart and kidney fibrosis possibly via targeting ASK1/MAPK (ERK, P38)/NF-κB signaling pathway. This finding extends our knowledge on the role of higenamine in cardiorenal fibrosis, providing a potential target to prevent the progression of CRS.

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