COVID-19 cardiac, vascular and renal impacts are frequent and massive in severe forms of the disease. Our project addresses the cellular and molecular basis of water and electrolytes balance alterations by describing the fates and functions of cardiovascular and renal cells during the course of the infection in a murine experimental model. Our project also aims at discriminating between direct viral injury and alterations due to the massive inflammation by comparing two mouse models expressing the SARS-Cov2 receptor, hACE2, either only in epithelial cells or in all Ace2-expressing cells. After viral infection of mice from both strains we will study the lung, cardiac and kidney structure and function. Pulmonary and cardiac vascular structure and leakage will be analyzed by immunofluorescence and vascular permeability and organ water content will be measured. Endothelial polarity will be analyzed by super-resolution microscopy and immunofluorescence studies of endothelial markers. Cardiac function will be assessed in vivo by echocardiography and electrocardiogram and coronary circulation will be studied ex vivo. Kidney function will be studied using metabolic cages to measure metabolites and ion excretion. Plasma levels of creatinine and hormones will be also determined as well as expression of ion transporters and their regulators. This project will help understanding the cardiovascular injuries that take place during the disease and will give us the basis to further study the cardiovascular consequences secondary to COVID-19.
