ADAMTS7, a target in atherosclerosis, cooperates with its homolog ADAMTS12 to protect against myxomatous valve degeneration.

ABSTRACT: The physiological roles of the metalloprotease-proteoglycan ADAMTS7, a drug target in atherosclerosis and vascular restenosis, and its homolog ADAMTS12, are undefined in the cardiovascular system. The objective of the present work was to investigate their roles in mice with genetic inactivation of both proteases and in relation to the resulting valve defects, to define their proteolytic activities in the matrisome. Here, we demonstrate that Adamts7 and Adamts12 are co-expressed in heart valves and each buffers inactivation of the other by compensatory upregulation. Leaflets of Adamts7 ^-/-;Adamts12 ^-/- aortic valves, but not the respective single mutants, were abnormally shaped at birth, with progressively severe disorganization and enlargem

SUBMITTER: Mead TJ 

PROVIDER: S-EPMC11925103 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature