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

Abstract

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.

Exploring the immunogenic properties of SARS-CoV-2 structural proteins: PAMP:TLR signaling in the mediation of the neuroinflammatory and neurologic sequelae of COVID-19

“…Clough et al found that the S protein increased expression of caspase 3/7 in human microglial cells suggesting increased apoptosis ( Clough et al, 2021 ). Huang et al found that the S protein induced nuclear fragmentation in cardiomyocytes, which is a prominent feature of cellular necrosis and apoptosis ( Huang et al, 2022 ). Consistent with the findings of Clough et al, Nuovo et al found that S1, but not S2 injected IV induces caspase-3 in mouse brain endothelial cells, suggesting increased apoptosis.…”

Self-assembly vascularized human cardiac organoids model cardiac diseases in petri dishes and in mice

“…RT-qPCR analysis of the post-transplanted COs confirmed the loss of cardiac muscle cells, evidenced by lower expression of TNNT2 and ACTN2. (41) Meanwhile, the fibrosis-related genes such as COL1A1, COL3A1, MMP-9, MMP-2 and α-SMA, (44)(45)(46) and genes that are related to inflammation: IL-1 β and IL-6 were detected to be upregulated after the spike 1+ang II treatment (Fig. 4F), which aligned with the physiological response within the human body.…”

The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells

“…The impact of SARS-CoV-2 Spike protein on cellular functions is of key interest, as the two mRNA vaccines BNT162b2 from Pfizer-BioNTech and mRNA-1273 from Moderna, generate high levels of this protein [14,[22][23][24]. Therefore, searching for circulating Spike in plasma of COVID-19 patient might help in understanding unexpected adverse effects following COVID-19 mRNA vaccination [8,12].…”

“…Relevant to this issue are reported evidences of circulating Spike Protein detected in post-COVID-19 mRNA vaccinated subjects [18][19][20][21][22][23], and several reports outlining that Sprotein affects cellular metabolism and gene expression in a variety of tissue systems [12,[24][25][26][27][28][29], including the hematopoietic system [28,29]. Accordingly, the effects of SARS-CoV-2 infection and/or vaccination on the hematopoietic system should be carefully considered [28][29][30].…”