Sars‐Cov‐2 Spike Protein‐Induced Damage of hiPSC‐Derived Cardiomyocytes. Issue 7 (6th May 2022)

• Record Type: Journal Article
• Authors: Huang, Xiaochen; Huang, Boxin; He, Yong; Feng, Liang; Shi, Jian; Wang, Li; Peng, Juan; Chen, Yong
• Is Part Of: Advanced biology. Volume 6:Issue 7(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-06
• Subjects: ACE2 -- Ang II -- cardiomyocytes -- hiPSC -- Sars‐Cov‐2 -- spike protein; Molecular biology -- Periodicals; Systems biology -- Periodicals; Biological systems -- Periodicals; Biotechnology -- Periodicals; Bioengineering -- Periodicals; Biomedical engineering -- Periodicals; 660.6
• DOI: 10.1002/adbi.202101327
• Languages: English
• ISSNs: 2701-0198

Abstract

Abstract: Sars‐Cov‐2 may trigger molecular and functional alterations of cardiomyocytes (CMs) of the heart due to the presence of receptor angiotensin‐converting enzyme 2 (ACE2) of the host cells. While the endocytic itinerary of the virus via cleavage of the spike protein of Sars‐Cov‐2 is well understood, the role of the remaining part of the spike protein subunit and ACE2 complex is still elusive. Herein, the possible effects of this complex are investigated by using synthetic spike proteins of Sars‐Cov‐2, human‐induced pluripotent stem cells (hiPSC), and a culture device made of an arrayed monolayer of cross‐linked nanofibers. hiPSCs are first differentiated into CMs that form cardiac tissue‐like constructs with regular beating and expression of both ACE2 and gap junction protein Connexin 43. When incubated with the spike proteins, the hiPSC‐CMs undergo a rhythmic fluctuation with overstretched sarcomere structures and dispersed gap junction proteins. When incubated with the spike proteins and supplementary angiotensin II, the damage of the spike protein on hiPSC‐CMs is enhanced due to downregulated ACE2, chromatin margination, altered Connexin 43 expression, sarcomere disruption, and beating break. This discovery may imply latent effects of the spike proteins on the heart. Abstract : The Sars‐Cov‐2 spike protein can affect the behavior of host cells. By using cardiomyocytes derived from human induced pluripotent stem cells, this study shows the clear effects of the spike protein on cardiac beating, sarcomere structure, and distribution of gap junction proteins. In the presence of supplementary angiotensin II, the effects become more evident, showing even a beating arrest of the cardiomyocytes.