SARS-CoV-2 spike protein exposure in human cardiomyocytes caused significant alterations in calcium dynamics and structural abnormalities, affecting gene expression.
Does SARS-CoV-2 spike protein induce structural, functional, and molecular abnormalities in human embryonic stem cell-derived cardiomyocytes?
SARS-CoV-2 spike protein directly induces structural, functional, and molecular abnormalities in human stem cell-derived cardiomyocytes, suggesting a direct pathogenic role in COVID-19-related cardiac injury.
Absolute Event Rate: 0% vs 0%
ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causative agent of COVID‐19, has resulted in more than 7.1 million deaths worldwide since 2019 and is increasingly recognized for its cardiovascular complications beyond respiratory disease. Growing evidence suggests that the SARS‐CoV‐2 spike protein itself, present during infection or after vaccination, may directly contribute to cardiac dysfunction, including myocarditis, through interaction with angiotensin‐converting enzyme 2 (ACE2) receptors expressed in cardiomyocytes. To investigate these effects, we established a lentiviral‐based SARS‐CoV‐2 pseudovirus system expressing spike proteins from the Wuhan and Delta variants and examined their impact on human embryonic stem cell–derived cardiomyocytes (ESC‐CMs). Exposure to pseudovirus resulted in significant increases in sarcomere length and promoted syncytium formation in ESC‐CMs. Moreover, infection with either Wuhan or Delta spike pseudoviruses caused marked early disturbances in intracellular calcium transient dynamics as early as 1.5 hours post‐infection, with partial recovery observed by 24 hours. Transcriptomic analyses further revealed significant dysregulation of key cardiac‐related genes involved in cell junction organization, structural integrity, ion channel function, and calcium handling. Together, these findings demonstrate the utility of a lentiviral pseudovirus platform for modeling SARS‐CoV‐2–induced cardiac injury and highlight a direct pathogenic role of the spike protein in cardiac structural, functional, and molecular abnormalities.
Huang et al. (Thu,) reported a other. SARS-CoV-2 spike protein exposure in human cardiomyocytes caused significant alterations in calcium dynamics and structural abnormalities, affecting gene expression.