Myogenin suppresses apoptosis induced by angiotensin II in human induced pluripotent stem cell-derived cardiomyocytes

  • Biochem Biophys Res Commun. 2021 May 7;552:84-90. doi: 10.1016/j.bbrc.2021.03.031.
Qiang Gao  1 ,  Ping Wang  2 ,  Hailong Qiu  1 ,  Bin Qiu  3 ,  Weijin Yi  3 ,  Wenchang Tu  3 ,  Bin Lin  4 ,  Daoheng Sun  3 ,  Rong Zeng  5 ,  Meiping Huang  6 ,  Jimei Chen  1 ,  Jianzheng Cen  7 ,  Jian Zhuang  8
Affiliations
  • 1. Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510100, China.
  • 2. School of Medical Imaging, Tianjin Medical University, Tianjin, 300203, China.
  • 3. Department of Mechanical & Electrical Engineering, Xiamen University, Xiamen, Fujian, 361102, China.
  • 4. Guangdong Beating Origin Regenerative Medicine Co. Ltd., Foshan, Guangdong, 528231, China.
  • 5. Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510100, China.
  • 6. Department of Catheterization Lab, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou, China.
  • 7. Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510100, China. Electronic address: [email protected].
  • 8. Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510100, China. Electronic address: [email protected].
PMID: 33743352 DOI: 10.1016/j.bbrc.2021.03.031
Abstract

Background: Angiotensin II (Ang II), an important component of the renin-angiotensin system (Ras), plays a critical role in the pathogenesis of cardiovascular disorders. In addition, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been considered as a promising platform for studying personalized medicine for heart diseases. However, whether Ang II can induce the Apoptosis of hiPSC-CMs is not known.

Methods: In this study, we treated hiPSC-CMs with different concentrations of Ang II [0 nM (vehicle as a control), 1 nM, 10 nM, 100 nM, 1 μM, 10 μM, 100 μM, and 1 mM] for various time periods (24 h, 48 h, 6 days, and 10 days) and analyzed the viability and Apoptosis of hiPSC-CMs.

Results: We found that treatment with 1 mM Ang II for 10 days reduced the viability of hiPSC-CMs by 41% (p = 2.073E-08) and increased Apoptosis by 2.74-fold, compared to the control group (p = 6.248E-12). MYOG, which encodes the muscle-specific transcription factor myogenin, was also identified as an apoptosis-suppressor gene in Ang II-treated hiPSC-CMs. Ectopic MYOG expression decreased the Apoptosis and increased the viability of Ang II-treated hiPSC-CMs. Further analysis of the RNA Sequencing (RNA-seq) data illustrated that myogenin ameliorated Ang II-induced Apoptosis of hiPSC-CMs by downregulating the expression of proinflammatory genes.

Conclusion: Our findings suggest that Ang II induces the Apoptosis of hiPSC-CMs and that myogenin attenuates Ang II-induced Apoptosis.

Keywords
Angiotensin II; Apoptosis; Cell viability; Human induced pluripotent stem cell-derived cardiomyocytes; MYOG.
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