2. Academic Validation
  3. An abnormal TRPV4-related cytosolic Ca2+ rise in response to uniaxial stretch in induced pluripotent stem cells-derived cardiomyocytes from dilated cardiomyopathy patients

An abnormal TRPV4-related cytosolic Ca2+ rise in response to uniaxial stretch in induced pluripotent stem cells-derived cardiomyocytes from dilated cardiomyopathy patients

  • Biochim Biophys Acta Mol Basis Dis. 2017 Nov;1863(11):2964-2972. doi: 10.1016/j.bbadis.2017.07.021.
Jun Lu 1,  Yee-Ki Lee 2,  Xinru Ran 2,  Wing-Hon Lai 2,  Ronald A Li 3,  Wendy Keung 4,  Kennis Tse 4,  Hung-Fat Tse 5,  Xiaoqiang Yao 6
Affiliations

Affiliations

  • 1 School of Biomedical Sciences and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
  • 2 Cardiology Division, Department of Medicine, The University of Hong Kong, Hong Kong, China; Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, The University of Hong Kong, Hong Kong, China; Guangzhou Institutes of Biomedicine and Health, China.
  • 3 Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Sweden; Dr. Li Dak-Sum Centre, The University of Hong Kong - Karolinska Institutet Collaboration in Regenerative Medicine, Hong Kong, China.
  • 4 Dr. Li Dak-Sum Centre, The University of Hong Kong - Karolinska Institutet Collaboration in Regenerative Medicine, Hong Kong, China.
  • 5 Cardiology Division, Department of Medicine, The University of Hong Kong, Hong Kong, China; Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, The University of Hong Kong, Hong Kong, China; Guangzhou Institutes of Biomedicine and Health, China; Shenzhen Institutes of Research and Innovation, The University of Hong Kong, Hong Kong, China. Electronic address: hftse@hku.hk.
  • 6 School of Biomedical Sciences and Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. Electronic address: yao2068@cuhk.edu.hk.
PMID: 28754452 DOI: 10.1016/j.bbadis.2017.07.021
Abstract

Dilated cardiomyopathy (DCM) is cardiac disease characterized by increased left ventricular chamber volume and decreased systolic function. DCM patient-specific human induced-pluripotent stem cells-derived cardiomyocytes (DCM-hiPSC-CMs) were generated. We found that uniaxial stretch elicited a cytosolic [CA2+]i rise in hiPSC-CMs. Compared to control-hiPSC-CMs, DCM-hiPSC-CMs displayed a greater magnitude of [CA2+]i responses to the cell stretch of 10-15% elongation in length. This stretch-induced [CA2+]i rise was abolished by removal of extracellular CA2+ and markedly attenuated by TRPV4 inhibitors HC-067047 and RN-1734. Application of nifedipine and tranilast also reduced the [CA2+]i response but to a lesser degree. Moreover, the augmented [CA2+]i was decreased by cytochalasin D treatment. Taken together, our study for the first time demonstrated an abnormal TRPV4-related mechanosensitive CA2+ signaling in DCM-hiPSC-CMs.

Keywords

Calcium signaling; Cell stretch; Dilated cardiomyopathy; Human induced pluripotent stem cells; TRPV4 channel.

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