2. Academic Validation
  3. Shear stress-induced Ca2+ influx triggers endoplasmic reticulum stress and cardiomyocyte apoptosis: implications for mitral regulation

Shear stress-induced Ca2+ influx triggers endoplasmic reticulum stress and cardiomyocyte apoptosis: implications for mitral regulation

  • Biol Res. 2026 Feb 8;59(1):17. doi: 10.1186/s40659-026-00671-4.
Wei-Ting Chang # 1 2 3,  Jun-Ming Su # 4,  Fan-E Mo 5,  Jhih-Yuan Shih # 6 7,  Wen-Tai Chiu # 8
Affiliations

Affiliations

  • 1 School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan.
  • 2 Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, No. 901, Zhong Hua Road, Yong Kang Dist., Tainan, Taiwan.
  • 3 College of Medicine, National Sun Yat-sen University, Kaohsiung, 804, Taiwan.
  • 4 Department of Biomedical Engineering, National Cheng Kung University, No. 1, University Road, Tainan, Taiwan.
  • 5 Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan.
  • 6 Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, No. 901, Zhong Hua Road, Yong Kang Dist., Tainan, Taiwan. [email protected].
  • 7 College of Medicine, National Sun Yat-sen University, Kaohsiung, 804, Taiwan. [email protected].
  • 8 Department of Biomedical Engineering, National Cheng Kung University, No. 1, University Road, Tainan, Taiwan. [email protected].
  • # Contributed equally.
PMID: 41656311 DOI: 10.1186/s40659-026-00671-4
Abstract

BACKGROUND: Mitral regurgitation is highly prevalent and elevates the risk of heart failure. Regurgitant flow induced shear stress disrupts Ca2+ homeostasis in atrial cardiomyocytes. Overloaded Ca2+ is a crucial regulator of endoplasmic reticulum stress-mediated Apoptosis, although the regulatory mechanisms remain unclear. We aimed to explore the relationship between shear stress and Ca2+ homeostasis. METHODS AND RESULTS: Through employing an in vitro model replicating atrial cardiomyocytes during mitral regurgitation, we observed that shear stress increased Ca2+ oscillation and the amplitude of Ca2+ waves through extracellular Ca2+ influx. Suppression of mechanosensitive Ca2+ channels or store-operated calcium entry resulted in decreased intracellular Ca2+ concentration and oscillation. Conversely, the inhibition of voltage-gated Ca2+ channels did not significantly impact the Ca2+ concentration. Remarkably, shear stress elevated the expression of endoplasmic reticulum stress and apoptosis-related proteins in HL-1 cells in a time-dependent manner. Also, in a novel rodent mitral regurgitation model, shear stress increased Apoptosis and endoplasmic reticulum stress expression compared to sham rats. CONCLUSIONS: Our findings underscore that shear stress induces Apoptosis through mechanosensitive and store-operated Ca2+ channels, leading to Ca2+ overload and endoplasmic reticulum stress. Understanding the mechanisms behind shear stress-disturbed Ca2+ homeostasis may enhance the treatment of mitral regurgitation-induced heart failure.

Keywords

Apoptosis; Ca2+ oscillation; ER stress; Heart failure; Mitral regurgitation; Shear stress.

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