The emerging Janus face of SVEP1 in development and disease.

Human genomic and proteomic data implicate Sushi, von Willebrand factor type A, epidermal growth factor, and pentraxin domain containing 1 (SVEP1) in the pathogenesis of human chronic disease, including cardiovascular disease, glaucoma, and dementia. SVEP1 is critical for vascular development and appears to promote aging, consistent with the antagonistic pleiotropy theory of aging. Many cell types adhere and/or proliferate in response to SVEP1, but the mechanisms underlying its role in development and disease are unclear. SVEP1 is contained within the extracellular matrix and circulates in plasma, making it a priority candidate for disease diagnostics, prognostics, and therapeutics. Sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1 (SVEP1) is a large extracellular matrix protein that is also detected in circulation. Recent plasma proteomic and genomic studies have revealed a large number of associations between SVEP1 and human traits, particularly chronic disease. These include associations with cardiac death and disease, diabetes, platelet traits, glaucoma, dementia, and aging; many of these are causal. Animal models demonstrate that SVEP1 is critical in vascular development and disease, but its molecular and cellular mechanisms remain poorly defined. Future studies should aim to characterize these mechanisms and determine the diagnostic, prognostic, and therapeutic value of measuring or intervening on this enigmatic protein. [ABSTRACT FROM AUTHOR]