Type 2 alveolar epithelial cell-derived circulating extracellular vesicle-encapsulated surfactant protein C as a mediator of cardiac inflammation in COVID-19

Abstract

Among the countless endeavours made at elucidating the pathogenesis of COVID-19, those aimed at the histopathological alterations of type 2 alveolar epithelial cells (AT2) are of outstanding relevance to the field of lung physiology, as they are the building blocks of the pulmonary alveoli. A merit of high regenerative and proliferative capacity, exocytotic activity resulting in the release of extracellular vesicles (EVs) is particularly high in AT2 cells, especially in those infected with SARS-CoV-2. These AT2 cell-derived EVs, containing the genetic material of the virus, might enter the bloodstream and make their way into the cardiovascular system, where they may infect cardiomyocytes and bring about a series of events leading to heart failure. As surfactant protein C, a marker of AT2 cell activity and a constituent of the lung surfactant complex, occurs abundantly inside the AT2-derived EVs released during the inflammatory stage of COVID-19, it could potentially be used as a biomarker for predicting impending heart failure in those patients with a history of cardiovascular disease.

Keywords: COVID-19; Cardiac inflammation; Extracellular vesicle; Surfactant protein C; Type 2 alveolar epithelial cell.

Fig. 1

A simplified diagram illustrating a proposed pathway for infection of cardiomyocytes with SARS-CoV-2 by means of COVID-19-associated type 2 alveolar epithelial cell-derived circulating extracellular vesicles through the pulmonary vein as a major route from the lungs to the heart. Once the alveolar epithelial cells lining the inner surface of pulmonary alveoli are infected with SARS-CoV-2, they release a substantial amount of extracellular vesicles containing SP-C, IL-6 and cleaved caspase 3. These AT2-derived EVs are then drained via small veins that ultimately join together to form the pulmonary veins, draining into the left atrium of the heart. Once inside the cardiac chamber, the three pro-inflammatory molecules, particularly SP-C, might induce cardiac inflammation or myocarditis, ultimately resulting in heart failure