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ADAMTS7: a Novel Therapeutic Target in Atherosclerosis

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Abstract

Purpose of Review

Genome-wide association studies have repeatedly linked the metalloproteinase ADAMTS7 to coronary artery disease. Here we aim to highlight recent findings surrounding the human genetics of ADAMTS7, novel mouse models that investigate ADAMTS7 function, and potential substrates of ADAMTS7 cleavage.

Recent Findings

Recent genome-wide association studies in coronary artery disease have replicated the GWAS signal for ADAMTS7 and shown that the signal holds true even across different ethnic groups. However, the direction of effect in humans remains unclear. A recent novel mouse model revealed that the proatherogenicity of ADAMTS7 is derived from its catalytic functions, while at the translational level, vaccinating mice against ADAMTS7 reduced atherosclerosis. Finally, in vitro proteomics approaches have identified extracellular matrix proteins as candidate substrates that may be causal for the proatherogenicity of ADAMTS7.

Summary

ADAMTS7 represents an enticing target for therapeutic intervention. The recent studies highlighted here have replicated prior findings, confirming the genetic link between ADAMTS7 and atherosclerosis, while providing further evidence in mice that ADAMTS7 is a targetable proatherogenic enzyme.

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Funding

This work was supported by an American Heart Association predoctoral fellowship to A.C. (909206), grants from the National Institutes of Health to M.P.R. (R01HL150359, R01HL166916, and UL1TR001873), a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute to R.C.B (R01HL141745), and institutional funds from Columbia University to R.C.B.

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  1. Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University, New York, NY, USA

    Allen Chung, Muredach P. Reilly & Robert C. Bauer

  2. Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA

    Muredach P. Reilly

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  1. Allen Chung
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Chung, A., Reilly, M.P. & Bauer, R.C. ADAMTS7: a Novel Therapeutic Target in Atherosclerosis. Curr Atheroscler Rep 25, 447–455 (2023). https://doi.org/10.1007/s11883-023-01115-0

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