Simona Scorza, Valentina Brunetti, Giorgia Scarpellino, Maira Certini, Andrea Gerbino, Francesco Moccia
Ca signaling events are essential for maintaining cardiovascular health, regulating critical functions in both endothelial and cardiac cells. SARS-CoV-2 infection impinges this delicate balance, leading to severe cardiovascular complications. SARS-CoV-2 binds to the ACE2 receptor on endothelial and cardiomyocyte surfaces, triggering abnormal increases in intracellular Ca levels that promote endothelial dysfunction, inflammation, and hypercoagulation. In endothelial cells, this dysregulation activates a pro-inflammatory state and compromises vascular integrity. In cardiomyocytes, SARS-CoV-2-induced Ca imbalances contribute to arrhythmias and heart failure by promoting abnormal Ca cycling and energy metabolism disruptions. Additionally, the cytokine storm associated with COVID-19 amplifies these effects by further altering Ca handling, enhancing inflammatory responses, and promoting thrombosis. Targeting Ca channels, particularly endolysosomal two-pore channels, represents a promising therapeutic approach to counteract SARS-CoV-2's effects on Ca dynamics. Several FDA-approved drugs that modulate Ca signaling could be repurposed to prevent viral entry and mitigate cardiovascular damage. Understanding these Ca-related mechanisms offers valuable insights for developing treatments to reduce cardiovascular risk in COVID-19 and potentially future viral infections impacting the cardiovascular system.
