Sars‐Cov‐2 Spike Protein‐Induced Damage of hiPSC‐Derived Cardiomyocytes

Xiaochen Huang (1) , Boxin Huang (1) , Yong He (1) , Liang Feng (1) , Jian Shi (2) , Li Wang (2) , Juan Peng (1) , Yong Chen (1)

1 PASTEUR - Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640)
2 MesoBioTech

Sars-Cov-2 may trigger molecular and functional alterations of cardiomyocytes 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, we investigate the possible effects of this complex 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 crosslinked nanofibers. hiPSCs were firstly differentiated into cardiomyocytes (CM) which formed 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 underwent 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 was 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.

Mots clés: Sars-Cov-2; Spike protein; hiPSC; Cardiomyocytes; ACE2; Ang II

Domaines: Maladies infectieuses; Maladies émergentes; Cardiologie et système cardiovasculaire

Xiaochen Huang, Boxin Huang, Yong He, Liang Feng, Jian Shi, et al.. Sars‐Cov‐2 Spike Protein‐Induced Damage of hiPSC‐Derived Cardiomyocytes. Advanced Biology, inPress, ⟨10.1002/adbi.202101327⟩. ⟨hal-03664385⟩