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Review
. 2023 Aug;25(8):447-455.
doi: 10.1007/s11883-023-01115-0. Epub 2023 Jun 24.

ADAMTS7: a Novel Therapeutic Target in Atherosclerosis

Allen Chung  1 , Muredach P Reilly  1   2 , Robert C Bauer  3
Affiliations
Review

ADAMTS7: a Novel Therapeutic Target in Atherosclerosis

Allen Chung et al. Curr Atheroscler Rep. 2023 Aug.

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. 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.

Keywords: ADAMTS7; Atherosclerosis; Coronary artery disease; Extracellular matrix; Genome-wide association studies; Smooth muscle cells.

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Conflict of interest statement

Competing Interests: The authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
LocusZoom plot of the 15q25.1 GWAS signal in CAD within people of European ancestry [2] The GWAS signal centers around ADAMTS7, with the histone acetyltransferase MORF4L1 lying immediately upstream of the gene. Downstream of ADAMTS7 lies a cluster of three nicotine receptors CHRNA3-A5-B4. Linkage disequilibrium is referenced to the lead SNP rs7173743. The coding S214P SNP (rs3825807) is highlighted in yellow. This figure was created using LocusZoom [56].
Fig. 2
Fig. 2
Proposed model for the mechanistic effect of ADAMTS7 on the vasculature. ADAMTS7 is induced in response to vascular injury. ADAMTS7 cleaves components of the ECM. This cleavage activity, in turn, leads to an increase in SMC migration through a yet unknown mechanism. It is unknown whether the elevated SMC migration or the cleaved ECM itself is causal for the associated increase in atherosclerosis. Created with BioRender.com
See this image and copyright information in PMC

References

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