To gain insights into the mechanisms driving cardiovascular complications in COVID-19, we performed a case-control plasma proteomics study in COVID-19 patients. Our results identify the senescence-associated secretory phenotype, a marker of biological aging, as the dominant process associated with disease severity and cardiac involvement. FSTL3, an indicator of senescence-promoting Activin/TGFβ signaling, and ADAMTS13, the von Willebrand Factor-cleaving protease whose loss-of-function causes microvascular thrombosis, were among the proteins most strongly associated with myocardial stress and injury. Findings were validated in a larger COVID-19 patient cohort and the hamster COVID-19 model, providing new insights into the pathophysiology of COVID-19 cardiovascular complications with therapeutic implications.
Keywords: ADAMTS13, A Disintegrin And Metalloproteinase with a Thrombospondin type 1 motif, member 13; COVID-19; FSTL3, follistatin-like 3; NT-proBNP, N-terminal pro–B-type natriuretic peptide; SASP, senescence associated secretory phenotype; TGFβ, transforming growth factor beta; hsTnT, high sensitivity troponin T; myocardial injury; proteomics; senescence.
© 2022 The Authors.