Affinage

ADAMTS7

A disintegrin and metalloproteinase with thrombospondin motifs 7 · UniProt Q9UKP4

Length
1686 aa
Mass
184.1 kDa
Annotated
2026-06-09
75 papers in source corpus 26 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADAMTS7 is a secreted, cell-surface-retained zinc metalloprotease-proteoglycan of the ADAM-TS family whose extracellular matrix proteolysis drives vascular disease, osteoarthritis, and ectopic tissue remodeling (PMID:10464288, PMID:19168437, PMID:25712206). The full-length protein (ADAMTS7B) is a chondroitin-sulfate-modified proteoglycan tethered near the cell surface through its ancillary and prodomains, and its catalytic activity requires furin-dependent multistep prodomain removal completed at the cell surface (PMID:15192113); a prodomain Ser-to-Pro variant (rs3825807) that impairs this maturation reduces substrate cleavage and is associated with protection from disease (PMID:23415669). ADAMTS7 cleaves an expanding set of matrix and regulatory substrates, including COMP/TSP-5 via its four C-terminal TSP motifs to promote VSMC migration and neointima formation (PMID:16585064, PMID:19168437), thrombospondin-1 to inhibit re-endothelialization and modulate angiogenesis (PMID:25712208, PMID:32005000), LTBP3/LTBP4 and EFEMP1/fibulin-3 (PMID:30926607, PMID:35283288), TIMP-1 to disinhibit MMP-9 and degrade plaque collagen (PMID:37675562), and complement factor H to potentiate complement activation in renal injury (PMID:36735376). In hyperlipidemic mice, Adamts7 loss reduces atherosclerotic and neointimal lesions, and epistasis experiments establish COMP and TSP-1 degradation as the proteolytic basis of its proatherogenicity (PMID:25712206, PMID:36562301); in smooth muscle cells it additionally drives foam cell formation through a non-proteolytic AP-1/PU.1/CD36 transcriptional axis that increases oxLDL uptake (PMID:41609669). In cartilage, ADAMTS7 is a PTHrP transcriptional target that inhibits chondrocyte differentiation and endochondral bone formation, acts as a GEP convertase, and forms a TNF-α/NF-κB positive-feedback loop driving osteoarthritis (PMID:19487464, PMID:20506400, PMID:23928557). ADAMTS7 functions redundantly with ADAMTS12 to suppress heterotopic ossification and myxomatous valve degeneration (PMID:29618652, PMID:40115634). TIMP-4 is its most potent endogenous inhibitor, and a structure-based selective small-molecule inhibitor (BAY-9835) has been developed against its catalytic domain (PMID:34587841, PMID:38348661).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Established ADAMTS7 as a new member of the ADAM-TS family, defining the multidomain architecture that would later explain its substrate targeting and cell-surface behavior.

    Evidence Primary structure determination and expression profiling during mouse embryogenesis

    PMID:10464288

    Open questions at the time
    • No enzymatic substrate identified
    • No tissue function assigned
  2. 2004 High

    Resolved how ADAMTS7 is processed and localized, showing it is a chondroitin-sulfate proteoglycan retained at the cell surface and activated by furin-dependent prodomain removal.

    Evidence Biochemical characterization, GAG analysis, furin inhibition and cleavage assays in HEK293F cells

    PMID:15192113

    Open questions at the time
    • Physiological ECM substrates beyond alpha-2-macroglobulin not yet defined
    • In vivo relevance of cell-surface retention untested
  3. 2006 High

    Identified COMP as the first matrix substrate and mapped the binding to ADAMTS7's C-terminal TSP motifs and COMP's EGF repeats, giving the protease a defined cartilage target.

    Evidence Yeast two-hybrid, GST pull-down, co-IP from native cartilage, in vitro digestion with domain mapping

    PMID:16585064

    Open questions at the time
    • In vivo consequence of COMP cleavage unknown at this stage
    • Did not address vascular roles
  4. 2009 High

    Connected ADAMTS7 to both cartilage and vascular biology, showing PTHrP-driven inhibition of endochondral ossification via GEP inactivation and injury-induced COMP degradation that promotes VSMC migration.

    Evidence Transgenic and PTHrP-knockout mice, rat carotid balloon injury, overexpression/knockdown, GEP cleavage and substrate rescue assays

    PMID:19168437 PMID:19487464

    Open questions at the time
    • Whether COMP is the sole relevant vascular substrate not yet resolved
    • Endogenous regulation of ADAMTS7 activity incompletely defined
  5. 2010 High

    Defined GEP as a competitive endogenous regulator that both binds ADAMTS7 and suppresses its TNF-α-induced expression, establishing a layer of substrate-protective control.

    Evidence Yeast two-hybrid, GST pull-down, co-IP, immunofluorescence, in vitro digestion with domain mapping

    PMID:20506400

    Open questions at the time
    • Relative importance of GEP versus other inhibitors in vivo unknown
  6. 2013 High

    Linked a CAD-associated coding variant to molecular mechanism, showing the rs3825807 prodomain Ser-to-Pro substitution impairs maturation and reduces COMP cleavage and VSMC migration.

    Evidence Genotype-stratified VSMC conditioned media, prodomain cleavage and migration assays

    PMID:23415669

    Open questions at the time
    • Causal in vivo link between variant and atherosclerosis not directly shown
    • Effect on other substrates untested
  7. 2013 High

    Established a TNF-α/NF-κB positive-feedback loop driving osteoarthritis, demonstrating cartilage-specific ADAMTS7 overexpression causes spontaneous OA-like disease.

    Evidence Cartilage-specific transgenic and knockdown mice, surgical OA model, NF-κB reporter assay

    PMID:23928557

    Open questions at the time
    • Direct transcriptional targets downstream of ADAMTS7 in feedback loop not defined
  8. 2015 High

    Provided definitive in vivo genetic validation of ADAMTS7 as proatherogenic and dissected substrate-specific effects: TSP-1 degradation inhibits re-endothelialization while COMP loss is dispensable for that effect.

    Evidence Adamts7-/-, Tsp1-/-, and COMP-/- mice in wire injury and hyperlipidemic models, LC-MS/MS secretome, double-KO epistasis, proliferation assays

    PMID:25712206 PMID:25712208 PMID:25921940

    Open questions at the time
    • Full substrate repertoire driving lesion formation not yet enumerated
    • Cell-type origin of pathogenic ADAMTS7 unresolved
  9. 2019 High

    Expanded the substrate landscape via unbiased N-terminomics, identifying LTBP3/LTBP4 cleavage, defining autolysis sites, and naming TIMP-4 the most potent endogenous inhibitor.

    Evidence TAILS proteomics of fibroblast secretome, N-terminal sequencing, in vitro cleavage with recombinant LTBP4, TIMP inhibitor panel

    PMID:30926607

    Open questions at the time
    • Functional consequence of LTBP cleavage on elastogenesis not directly tested
  10. 2022 High

    Broadened the vascular substrate set with catalytic-dead-controlled proteomics, identifying 16 substrates including EFEMP1/fibulin-3 with a defined cleavage site.

    Evidence TAILS comparing WT vs E373Q ADAMTS7 in VSMCs and ECs, in vitro binary cleavage of purified EFEMP1

    PMID:35283288

    Open questions at the time
    • In vivo phenotypic relevance of each new substrate not established
  11. 2022 High

    Demonstrated therapeutic and mechanistic proof by vaccination, showing anti-ADAMTS7 antibodies block COMP and TSP-1 degradation and reduce disease across models, confirming these substrates as the proatherogenic basis.

    Evidence Murine ligation, wire injury, ApoE-/- and LDLR-/- atherosclerosis, swine stent model, in vitro cleavage with vaccine-derived antibodies

    PMID:36562301

    Open questions at the time
    • Durability and off-target effects of vaccination not addressed in timeline
  12. 2023 High

    Revealed two new pathogenic axes: TIMP-1 degradation that disinhibits MMP-9 and increases plaque collagen turnover, and complement factor H degradation that potentiates complement-driven renal injury.

    Evidence MS of plaques, co-IP, FRET PPI, in vitro degradation with MMP-9 readout; interactome, domain mapping, Adamts7-/- SLE/IR models with AAV-CFH rescue

    PMID:36735376 PMID:37675562

    Open questions at the time
    • Relative contribution of TIMP-1 versus matrix substrates to plaque stability not quantified
  13. 2024 High

    Identified a non-proteolytic transcriptional mechanism in which ADAMTS7 increases chromatin accessibility to drive an AP-1/PU.1/CD36 axis promoting SMC foam cell formation, and showed cell-type-specific transgenic but not knockout effects.

    Evidence SMC- and EC-specific conditional KO/transgenic mice, RNA-seq, ATAC-seq, oxLDL uptake assays, human carotid scRNA-seq

    PMID:41609669

    Open questions at the time
    • How a secreted protease alters intracellular chromatin accessibility mechanistically unresolved
    • Knockout failing to reduce disease versus prior whole-body KO data not reconciled in timeline
  14. 2024 High

    Delivered the first structure-based selective inhibitor, using an ADAMTS7 catalytic-domain co-crystal to design BAY-9835 that exploits differences from MMP12.

    Evidence X-ray crystallography, homology modeling, medicinal chemistry, in vitro enzymatic inhibition

    PMID:38348661

    Open questions at the time
    • In vivo efficacy not reported in this study
  15. 2024 Low

    Provided regulatory-genomic context for the CAD locus, linking rs4887091 to a CTCF site and 3D chromatin interactome controlling ADAMTS7 expression in coronary SMCs.

    Evidence snRNA-seq + snATAC-seq from human coronary arteries, caQTL, Hi-C (preprint)

    Open questions at the time
    • No direct functional validation of the variant's effect on ADAMTS7
    • Preprint, not peer reviewed
  16. 2025 High

    Established functional redundancy with ADAMTS12 in cardiovascular and connective tissue, showing double-knockout-specific heterotopic ossification and myxomatous valve degeneration with substrate accumulation.

    Evidence Single and double Adamts7/Adamts12 KO mice, electron microscopy, SLRP measurements, echocardiography, TAILS, TGFβ analysis

    PMID:29618652 PMID:40115634

    Open questions at the time
    • Molecular basis of compensation between the two proteases not defined
    • Direct substrate driving valve degeneration not pinpointed
  17. 2026 Medium

    Extended ADAMTS7 induction and downstream pathology to new contexts: cigarette-smoke CCL17/CCR4 signaling upregulates vascular ADAMTS7, BAY-9835 protects the post-infarct heart via NF-κB/pyroptosis suppression, and ADAMTS7 promotes cerebral MMP-9 activation worsening stroke outcomes.

    Evidence Cigarette smoke and HFD mouse models, recombinant CCL17, CCR4 siRNA, LAD ligation and MCAO, BAY-9835 pharmacology, transcriptomics (one preprint)

    PMID:41968389 PMID:42061659

    Open questions at the time
    • CCL17/CCR4 result is a single-lab preprint awaiting peer review
    • Direct substrate underlying cardioprotective and cerebral MMP-9 effects not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a secreted, cell-surface protease executes the non-proteolytic intracellular chromatin/AP-1/PU.1/CD36 program, and which specific substrate cleavages dominate each disease context, remain unresolved.
  • Mechanism coupling extracellular ADAMTS7 to nuclear chromatin remodeling unknown
  • Discordance between conditional-KO and whole-body-KO atherosclerosis phenotypes unexplained
  • Hierarchy of substrate importance across vascular, renal, cardiac, and cerebral pathology undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016787 hydrolase activity 3 GO:0005198 structural molecule activity 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 2 GO:0031012 extracellular matrix 2 GO:0005829 cytosol 1
Pathway
R-HSA-1474244 Extracellular matrix organization 6 R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 2
Partners
CFHCOMPEFEMP1GRNLTBP4THBS1TIMP1TIMP4

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 ADAMTS7 (ADAM-TS7) was identified as a novel zinc metalloprotease with a domain organization comprising a preproregion, a reprolysin-type catalytic domain, a disintegrin-like domain, a thrombospondin type-1 (TS) module, a cysteine-rich domain, a spacer domain, and a C-terminal TS module, placing it in the ADAM-TS family of reprolysin-like metalloproteases. Primary structure determination, genomic distribution analysis, expression profiling during mouse embryogenesis The Journal of biological chemistry High 10464288
2004 ADAMTS7B, the full-length product of the ADAMTS7 gene, is a proteoglycan modified by chondroitin sulfate attachment within a unique mucin domain, is retained near the cell surface via interactions involving the ancillary domain and prodomain, undergoes furin-dependent multistep prodomain removal (with final cleavage at the cell surface after Arg220), and is an active metalloproteinase capable of cleaving alpha-2-macroglobulin but does not cleave versican or aggrecan. Protein characterization, glycosaminoglycan analysis, furin inhibition assay, in vitro cleavage assay, subcellular localization studies in HEK293F cells The Journal of biological chemistry High 15192113
2006 ADAMTS-7 directly binds to and degrades cartilage oligomeric matrix protein (COMP); binding is mediated by the EGF repeat domain of COMP and the four C-terminal TSP motifs of ADAMTS-7; the recombinant catalytic domain and intact ADAMTS-7 cleave COMP in vitro in a Zn2+- and pH-dependent manner (optimal pH 7.5–9.5). Yeast two-hybrid screen, in vitro GST pull-down, co-immunoprecipitation from native articular cartilage, in vitro digestion assay, domain-mapping experiments FASEB journal High 16585064
2008 ADAMTS-7 cleaves alpha-2-macroglobulin (α2M) in vitro, generating 180- and 105-kDa cleavage products; α2M in turn inhibits ADAMTS-7-mediated COMP degradation in a concentration-dependent manner, representing the first identified endogenous inhibitor of ADAMTS-7. In vitro digestion assay, siRNA knockdown in human chondrocytes, blocking antibodies in cartilage explants Osteoarthritis and cartilage High 18485748
2009 ADAMTS-7 mediates vascular smooth muscle cell (VSMC) migration and neointima formation; ADAMTS-7 protein accumulates in neointima after balloon injury; TNF-α and PDGF-BB induce ADAMTS-7 expression; ADAMTS-7 facilitates VSMC migration through degradation of COMP, its vascular ECM substrate; COMP replenishment circumvents the pro-migratory effect. Rat carotid artery balloon injury model, adenovirus overexpression, siRNA knockdown in vivo and in vitro, VSMC migration/invasion assays, immunohistochemistry Circulation research High 19168437
2009 ADAMTS-7 is a direct transcriptional target of PTHrP signaling in chondrocytes; it inhibits chondrocyte differentiation and endochondral bone formation in a proteolytic activity-dependent manner; the cysteine-rich domain is required for ECM interaction; the C-terminal four TSP motifs are required for full proteolytic activity; ADAMTS-7 associates with and proteolytically inactivates GEP (granulin-epithelin precursor), acting as a GEP convertase to neutralize GEP-stimulated endochondral bone formation. Transgenic mice, PTHrP knockout mice, ADAMTS-7 overexpression/knockdown, reporter gene assay, domain-deletion constructs, in vitro GEP cleavage assay Molecular and cellular biology High 19487464
2010 Granulin-epithelin precursor (GEP) directly binds ADAMTS-7 via its C-terminal four TSP motifs (ADAMTS-7 side) and each granulin unit (GEP side); GEP co-localizes with ADAMTS-7 on the chondrocyte cell surface; GEP inhibits ADAMTS-7-mediated COMP degradation through competitive inhibition via direct protein-protein interactions and by suppressing TNF-α-induced ADAMTS-7 expression. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, immunofluorescence co-localization, in vitro digestion assay, domain-mapping Arthritis and rheumatism High 20506400
2013 A non-synonymous SNP rs3825807 (Ser-to-Pro substitution) in the ADAMTS7 prodomain reduces prodomain cleavage/maturation of the protease in VSMCs, resulting in less cleaved thrombospondin-5 (COMP/TSP-5) in conditioned media and reduced VSMC migratory ability; the protective G allele is associated with reduced ADAMTS7 function. Genotyped VSMC conditioned media analysis, prodomain cleavage assays, VSMC migration assays in cells stratified by genotype American journal of human genetics High 23415669
2013 ADAMTS-7 and TNF-α form a positive feedback loop in osteoarthritis: TNF-α induces ADAMTS-7 expression via NF-κB signaling, while ADAMTS-7 overexpression upregulates TNF-α and metalloproteinases; cartilage-specific ADAMTS-7 overexpression leads to chondrodysplasia and spontaneous OA-like phenotype; knockdown attenuates OA progression. Cartilage-specific ADAMTS-7 transgenic mice, siRNA knockdown mice, surgically-induced OA model, NF-κB reporter gene assay, immunohistochemistry Annals of the rheumatic diseases High 23928557
2015 ADAMTS-7 inhibits re-endothelialization of injured arteries by degrading thrombospondin-1 (TSP-1); ADAMTS-7 directly associates with TSP-1 via its C-terminus and degrades TSP-1 in vivo and in vitro; Adamts7-/- mice show greatly promoted re-endothelialization and reduced neointima formation; the inhibitory effect of ADAMTS-7 on endothelium recovery is abolished in Tsp1-/- mice (but not in COMP-/- mice), demonstrating TSP-1 as the relevant substrate for this effect. Adamts7-/- and Tsp1-/- mouse wire injury models, Evans blue staining, label-free LC-MS/MS secretome analysis, in vitro co-association and degradation assays, endothelial cell proliferation/migration assays Circulation High 25712208
2015 Adamts7 knockout in hyperlipidemic mouse models (Ldlr-/- and Apoe-/-) significantly reduces atherosclerotic lesion formation and neointimal formation; ADAMTS7 is proatherogenic; ADAMTS7 co-localizes with smooth muscle cell markers in human CAD lesions and localizes to the cytoplasm and cell membrane in cultured VSMCs, co-localizing with podosome markers; primary Adamts7-/- VSMCs show reduced migration under TNF-α stimulation. Whole-body knockout mice crossed to hyperlipidemic backgrounds, femoral wire injury model, VSMC migration assays, subcellular localization studies, immunohistochemistry of human lesions Circulation High 25712206
2019 TAILS unbiased substrate profiling identified LTBP3 and LTBP4 as ADAMTS7 substrates; ADAMTS7 cleaves LTBP4 at multiple sites in an N-terminal linker region connecting fibulin-5/tropoelastin and fibrillin-1-binding regions; ADAMTS7 undergoes autolysis at Glu729-Val730 and Glu732-Ala733 in the Spacer domain; TIMP-4 is the most potent endogenous inhibitor of ADAMTS7 (compared to TIMP-1, -2, -3). TAILS proteomic substrate analysis of human fibroblast secretome, N-terminal sequencing, Western blotting, in vitro cleavage assay with purified ADAMTS7 and recombinant LTBP4, metalloprotease inhibitor panel The Journal of biological chemistry High 30926607
2019 Wnt/β-catenin signaling (induced by IL-1β or Wnt7B) drives ADAMTS-7 expression in osteoarthritis synovial fibroblasts, and ADAMTS-7 from synovial fibroblasts contributes to COMP degradation in cartilage; blockade of Wnt signaling by DKK1 reduces ADAMTS-7 expression and COMP degradation. OA synovial fibroblast cultures, ERK inhibition, DKK1 Wnt pathway blockade, COMP degradation assays Journal of cellular and molecular medicine Medium 30903650
2022 TAILS in vascular smooth muscle and endothelial cells identified 24 unique cleavage sites from 16 protein substrates of ADAMTS7; EFEMP1 (Fibulin-3) was identified as an ADAMTS7 substrate with a preferred cleavage site at amino acids 123–124, validated by in vitro binary cleavage assay with purified EFEMP1. TAILS with ADAMTS7 WT vs. catalytic mutant (E373Q) adenovirus expression in VSMCs and ECs, in vitro binary cleavage assay with purified EFEMP1 Molecular & cellular proteomics High 35283288
2022 Vaccination with a peptide (ATS7vac) derived from ADAMTS7 generates specific antibodies that inhibit ADAMTS-7-mediated COMP and TSP-1 degradation, suppress VSMC migration, and promote re-endothelialization, confirming COMP and TSP-1 degradation as the mechanistic basis of ADAMTS7 proatherogenicity. Murine carotid artery ligation, wire injury, atherosclerosis models (ApoE-/- and LDLR-/-), swine coronary stent model, in vitro substrate cleavage assays with vaccination-derived antibodies Circulation High 36562301
2023 ADAMTS-7 binds to and degrades TIMP-1 via its catalytic domain; ADAMTS-7-mediated TIMP-1 degradation reduces TIMP-1's inhibitory capacity on MMP-9, leading to increased MMP-9 activity and collagen degradation in atherosclerotic plaques; Adamts7-/- atherosclerotic aortas show higher TIMP-1 levels and greater collagen content. Mass spectrometry of atherosclerotic plaques from Apoe-/- vs. Apoe-/-Adamts7-/- mice, co-immunoprecipitation, FRET-based protein-protein interaction assay, in vitro degradation assay, Picrosirius red collagen staining Circulation research High 37675562
2023 ADAMTS7 binds to complement factor H (CFH) at CCP domains 1–4 and degrades the CCP 1–7 domain through multiple cleavages; ADAMTS7 deficiency alleviates complement activation and related renal pathologies in lupus nephritis and renal ischemia-reperfusion injury models; adeno-associated virus-mediated CFH silencing abolished the protective effects of ADAMTS7 knockout, establishing the ADAMTS7→CFH degradation→complement activation axis. Unbiased interactome of lupus mice kidneys, in vitro cleavage assay, Adamts7-/- mouse models of SLE and renal I/R injury, AAV-mediated CFH silencing rescue experiment Journal of the American Society of Nephrology High 36735376
2018 ADAMTS7 and ADAMTS12 together protect against heterotopic ossification (HO) in hindlimb tendons, menisci, and ligaments; Adamts7-/-Adamts12-/- double-knockout mice (but not single knockouts) develop progressive HO, accompanied by abnormal collagen fibrils and reduced levels of the SLRPs biglycan, fibromodulin, and decorin, implicating these proteoglycans as downstream mediators. Single and double knockout mouse models, histology, collagen fibril analysis by electron microscopy, SLRP protein level measurements JCI insight High 29618652
2024 ADAMTS7 promotes smooth muscle cell (SMC) foam cell formation and atherosclerosis via an AP-1/PU.1/CD36 regulatory axis: ADAMTS7 expression increases chromatin accessibility at AP-1-enriched regions, upregulating PU.1 (a myeloid transcription factor), which in turn increases CD36 expression and oxidized LDL uptake by SMCs; SMC-specific and EC-specific Adamts7 conditional transgenic mice both show increased atherosclerosis, whereas conditional knockout in either cell type does not reduce atherosclerosis. SMC- and EC-specific conditional KO and transgenic mice, RNA-seq, ATAC-seq with motif analysis, oxLDL uptake assays, single-cell RNA-seq of human carotid atherosclerosis The Journal of clinical investigation High 41609669
2024 BAY-9835, the first orally bioavailable selective ADAMTS7 inhibitor, was designed using X-ray co-crystal structure of the ADAMTS7 catalytic domain to exploit amino acid differences between ADAMTS7 and MMP12 binding sites; the compound selectively inhibits the ADAMTS7 catalytic zinc-containing metalloproteinase domain. X-ray crystallography co-crystal structure, in silico homology modeling, medicinal chemistry optimization, in vitro enzymatic inhibition assays Journal of medicinal chemistry High 38348661
2021 A fluorogenic FRET substrate (ATS7FP7) was developed for ADAMTS7 activity measurement; TIMP-4 shows the highest inhibitory potency among TIMPs for ADAMTS7 (confirmed with both fluorogenic substrate and SDS-PAGE assay using LTBP4S-A), supporting TIMP-4 as the primary physiological inhibitor. Fluorogenic FRET substrate assay development, inhibition constant measurements for TIMP-1/-2/-3/-4 and hydroxamate inhibitors Journal of enzyme inhibition and medicinal chemistry Medium 34587841
2015 ADAMTS-7 promotes VSMC proliferation in vitro and in vivo; adenoviral ADAMTS-7 overexpression increases the percentage of PCNA-positive cells in intima and media after injury; siRNA knockdown reduces intimal VSMC replication; [3H]-thymidine incorporation assay shows 61% enhanced and 23% reduced replication with overexpression and knockdown respectively. Rat carotid artery injury model with adenoviral delivery, perivascular siRNA administration, [3H]-thymidine incorporation assay in primary VSMCs, PCNA immunostaining Science China. Life sciences Medium 25921940
2020 ADAMTS7 promotes angiogenesis in endothelial cells via TSP-1 degradation: ADAMTS7 knockdown attenuates EC migration and tube formation; ADAMTS7-Ser214 overexpression increases these; proteomics shows inverse TSP-1 levels in conditioned media correlating with ADAMTS7 status; the pro-angiogenic effect is abolished by a TSP-1 blocking antibody; the Ser214Pro substitution (CAD-protective variant) reduces TSP-1 degrading activity. ADAMTS7 knockdown/overexpression in ECs, proteomics of conditioned media, TSP-1 cleavage assay, tube formation and migration assays, TSP-1 blocking antibody rescue Atherosclerosis Medium 32005000
2025 ADAMTS7 and ADAMTS12 are co-expressed in heart valves and each compensates for loss of the other by upregulation; Adamts7-/-Adamts12-/- double knockout mice develop myxomatous aortic valve degeneration with ECM substrate accumulation including periostin; TAILS identified shared and distinct ECM substrates/cleavage sites for each protease; TGFβ signaling was increased in mutant valves. Adamts7-/-Adamts12-/- double knockout mice, Doppler echocardiography, N-terminomics TAILS from secretome libraries, immunostaining, TGFβ pathway analysis Journal of molecular and cellular cardiology plus High 40115634
2026 Cigarette smoke exposure upregulates vascular ADAMTS7 expression via CCL17/CCR4 signaling: cigarette smoke induces CCL17 in lungs and plasma; recombinant CCL17 upregulates ADAMTS7 in VSMCs; CCR4 silencing blocks this upregulation; conditioned media from CCL17-stimulated ADAMTS7-deficient VSMCs shows reduced inflammatory cytokine release by endothelial cells and reduced monocyte-to-EC adhesion; in Apoe-/- mice, smoking-induced plaque inflammation is blunted in Apoe-/-Adamts7-/- mice. Murine cigarette smoke exposure model, bulk RNA-seq of lung, recombinant CCL17 treatment of VSMCs, CCR4 siRNA knockdown, conditioned media EC activation assay, Apoe-/-Adamts7-/- double KO atherosclerosis model bioRxivpreprint Medium
2024 The rs4887091 variant within the ADAMTS7 CAD GWAS locus alters a CTCF binding site and modulates function of a super chromatin interactome in coronary artery smooth muscle cells, linking the disease variant to ADAMTS7 gene regulation through 3D chromatin conformation. Single-nucleus gene expression and chromatin accessibility profiling (snRNA-seq + snATAC-seq) from 44 human coronary arteries, caQTL mapping, Hi-C chromatin conformation capture bioRxivpreprint Low
2026 Pharmacological inhibition of ADAMTS7 with BAY-9835 improves left ventricular systolic function and reduces infarct size after AMI in mice; transcriptomic analysis identified the NF-κB/pyroptosis pathway as a downstream mechanism; BAY-9835 inhibits P65 phosphorylation and pyroptosis marker expression; NF-κB activation abolishes BAY-9835 protection. LAD ligation AMI mouse model, oxygen-glucose deprivation in AC16 cardiomyocytes, transcriptomic analysis, NF-κB pathway pharmacological activation/inhibition, echocardiography Toxicology and applied pharmacology Medium 42061659
2026 In a high-fat diet mouse model, ADAMTS-7 promotes MMP-9 activation in cerebral vessels; ADAMTS-7 shRNA knockdown attenuates HFD-induced MMP-9 activity, reduced middle cerebral arterial diameter, and worsened neurological outcomes after MCAO; ADAMTS-7 is expressed in neurons, astrocytes, oligodendrocytes, and blood vessels in the brain. HFD mouse model, MCAO, lentiviral shRNA knockdown, Western blotting, immunostaining, cerebral vascular casting CNS neuroscience & therapeutics Medium 41968389

Source papers

Stage 0 corpus · 75 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet (London, England) 423 21239051
2009 ADAMTS-7 mediates vascular smooth muscle cell migration and neointima formation in balloon-injured rat arteries. Circulation research 185 19168437
1999 ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases. General features and genomic distribution of the ADAM-TS family. The Journal of biological chemistry 172 10464288
2006 ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 135 16585064
2015 ADAMTS-7 inhibits re-endothelialization of injured arteries and promotes vascular remodeling through cleavage of thrombospondin-1. Circulation 128 25712208
2010 Granulin-epithelin precursor binds directly to ADAMTS-7 and ADAMTS-12 and inhibits their degradation of cartilage oligomeric matrix protein. Arthritis and rheumatism 115 20506400
2008 Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin. Osteoarthritis and cartilage 114 18485748
2015 Knockout of Adamts7, a novel coronary artery disease locus in humans, reduces atherosclerosis in mice. Circulation 109 25712206
2009 ADAMTS-7, a direct target of PTHrP, adversely regulates endochondral bone growth by associating with and inactivating GEP growth factor. Molecular and cellular biology 95 19487464
2013 ADAMTS7 cleavage and vascular smooth muscle cell migration is affected by a coronary-artery-disease-associated variant. American journal of human genetics 89 23415669
2004 ADAMTS7B, the full-length product of the ADAMTS7 gene, is a chondroitin sulfate proteoglycan containing a mucin domain. The Journal of biological chemistry 80 15192113
2009 The role of ADAMTS-7 and ADAMTS-12 in the pathogenesis of arthritis. Nature clinical practice. Rheumatology 73 19098927
2013 ADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis. Annals of the rheumatic diseases 69 23928557
2022 Peptide Vaccine Against ADAMTS-7 Ameliorates Atherosclerosis and Postinjury Neointima Hyperplasia. Circulation 61 36562301
2019 Proteomic discovery of substrates of the cardiovascular protease ADAMTS7. The Journal of biological chemistry 49 30926607
2017 Loss of Cardioprotective Effects at the ADAMTS7 Locus as a Result of Gene-Smoking Interactions. Circulation 46 28461624
2023 ADAMTS-7 Modulates Atherosclerotic Plaque Formation by Degradation of TIMP-1. Circulation research 45 37675562
2018 The metalloproteinase-proteoglycans ADAMTS7 and ADAMTS12 provide an innate, tendon-specific protective mechanism against heterotopic ossification. JCI insight 42 29618652
2012 Negative effects of ADAMTS-7 and ADAMTS-12 on endplate cartilage differentiation. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 36 22247065
2017 ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis. Scientific reports 35 28623250
2015 The Function and Roles of ADAMTS-7 in Inflammatory Diseases. Mediators of inflammation 28 26696755
2015 IL-17A enhances ADAMTS-7 expression through regulation of TNF-α in human nucleus pulposus cells. Journal of molecular histology 26 26446668
2019 Wnt and RUNX2 mediate cartilage breakdown by osteoarthritis synovial fibroblast-derived ADAMTS-7 and -12. Journal of cellular and molecular medicine 25 30903650
2010 ADAMTS-7, a novel proteolytic culprit in vascular remodeling. Sheng li xue bao : [Acta physiologica Sinica] 23 20717629
2013 Biochemistry and physiological functions of ADAMTS7 metalloprotease. Advances in biochemistry 22 24222922
2011 Expression of ADAMTS-7 and ADAMTS-12 in the nucleus pulposus during degeneration of rat caudal intervetebral disc. The Journal of veterinary medical science 22 21869572
2015 ADAMTS-7 promotes vascular smooth muscle cells proliferation in vitro and in vivo. Science China. Life sciences 21 25921940
2017 Genetic Variation at the ADAMTS7 Locus is Associated With Reduced Severity of Coronary Artery Disease. Journal of the American Heart Association 20 29089340
2015 ADAMTS-7 exhibits elevated expression in cartilage of osteonecrosis of femoral head and has a positive correlation with TNF- α and NF- κ B P65. Mediators of inflammation 18 25653475
2015 Association between plasma ADAMTS-7 levels and ventricular remodeling in patients with acute myocardial infarction. European journal of medical research 18 25885961
2013 ADAMTS7: a promising new therapeutic target in coronary heart disease. Expert opinion on therapeutic targets 18 23829786
2022 TAILS Identifies Candidate Substrates and Biomarkers of ADAMTS7, a Therapeutic Protease Target in Coronary Artery Disease. Molecular & cellular proteomics : MCP 16 35283288
2016 Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease. Physiological genomics 16 27614204
2014 ADAMTS-7 expression increases in the early stage of angiotensin II-induced renal injury in elderly mice. Kidney & blood pressure research 16 24642842
2019 Upregulation of miR‑423 improves autologous vein graft restenosis via targeting ADAMTS‑7. International journal of molecular medicine 13 31894258
2017 Genetic variants rs1994016 and rs3825807 in ADAMTS7 affect its mRNA expression in atherosclerotic occlusive peripheral arterial disease. Journal of clinical laboratory analysis 12 28205274
2017 Upregulation of ADAMTS‑7 and downregulation of COMP are associated with aortic aneurysm. Molecular medicine reports 12 28849199
2023 ADAMTS7: a Novel Therapeutic Target in Atherosclerosis. Current atherosclerosis reports 11 37354304
2016 Association of ADAMTS-7 Levels with Cardiac Function in a Rat Model of Acute Myocardial Infarction. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 11 26938210
2015 ADAMTS7 locus confers high cross-race risk for development of coronary atheromatous plaque. Molecular genetics and genomics : MGG 11 26189211
2023 ADAMTS-7 deficiency attenuates thoracic aortic aneurysm and dissection in mice. Journal of molecular medicine (Berlin, Germany) 10 36662289
2021 Development of a fluorogenic ADAMTS-7 substrate. Journal of enzyme inhibition and medicinal chemistry 10 34587841
2016 Classification of ADAMTS binding sites: The first step toward selective ADAMTS7 inhibitors. Biochemical and biophysical research communications 10 26872430
2024 BAY-9835: Discovery of the First Orally Bioavailable ADAMTS7 Inhibitor. Journal of medicinal chemistry 9 38348661
2022 miR-654-5p Suppresses Migration and Proliferation of Vascular Smooth Muscle Cells by Targeting ADAMTS-7. Cells, tissues, organs 9 35462367
2020 Association of polymorphisms in ADAMTS-7 gene with the susceptibility to coronary artery disease - a systematic review and meta-analysis. Aging 9 33122452
2020 Effect of a coronary-heart-disease-associated variant of ADAMTS7 on endothelial cell angiogenesis. Atherosclerosis 8 32005000
2020 Hypomethylation of DNA promoter upregulates ADAMTS7 and contributes to HTR-8/SVneo and JEG-3 cells abnormalities in pre-eclampsia. Placenta 8 32250736
2023 ADAMTS7-Mediated Complement Factor H Degradation Potentiates Complement Activation to Contributing to Renal Injuries. Journal of the American Society of Nephrology : JASN 7 36735376
2020 ADAMTS7 degrades Comp to fuel BMP2-dependent osteogenic differentiation and ameliorate oncogenic potential in osteosarcomas. FEBS open bio 7 32692461
2019 Genetic variants of ADAMTS7 confer risk for ischaemic stroke in the Chinese population. Aging 6 31460868
2018 Association of serum ADAMTS7 levels and genetic variant rs1994016 with acute coronary syndrome in a Chinese population: A case control study. Atherosclerosis 6 29980058
2023 New Markers for Cardiovascular Disease in Psoriatic Patients: Preliminary Study on Monocyte Phenotype, ADAMTS7, and mTOR Activity. Metabolites 5 36677041
2019 Upregulation of ADAMTS‑7 and downregulation of COMP are associated with spontaneous abortion. Molecular medicine reports 5 30720083
2025 ADAMTS7, a target in atherosclerosis, cooperates with its homolog ADAMTS12 to protect against myxomatous valve degeneration. Journal of molecular and cellular cardiology plus 4 40115634
2024 ADAMTS7 Promotes Smooth Muscle Foam Cell Expansion in Atherosclerosis. bioRxiv : the preprint server for biology 4 38463994
2023 Non-Canonical WNT/Wnt5a Pathway Activity in Circulating Monocytes of Untreated Psoriatic Patients: An Exploratory Study of Its Association with Inflammatory Cytokines and Cardiovascular Risk Marker-ADAMTS7. Biomedicines 4 36831113
2024 The Association of ADAMTS7 Gene Polymorphisms with the Risk of Coronary Artery Disease Occurrence and Cardiovascular Survival in the Polish Population: A Case-Control and a Prospective Cohort Study. International journal of molecular sciences 3 38396951
2024 Diagnostic value of serum COMP and ADAMTS7 for intervertebral disc degeneration. European journal of medical research 3 38528617
2024 Design, synthesis and biological evaluation of arylsulfonamides as ADAMTS7 inhibitors. RSC medicinal chemistry 3 39149096
2024 Association Between Plasma ADAMTS-7 Levels and Diastolic Dysfunction in Patients with Type 2 Diabetes Mellitus. Medicina (Kaunas, Lithuania) 3 39768861
2023 The rs3825807 Polymorphism of ADAMTS7 as a Potential Genetic Marker for Myocardial Infarction in Slovenian Subjects with Type 2 Diabetes Mellitus. Genes 3 36833435
2018 Expression of ADAMTS-7 in myocardial dystrophy associated with white muscle disease in lambs. Polish journal of veterinary sciences 3 29624002
2025 ADAMTS7 Enhances Gastric Cancer Growth and Metastasis by Triggering the NF-κB Signaling Pathway. Journal of Cancer 2 39781347
2021 Investigating ADAMTS7 and ADAMTS12 levels in prediabetic and Type 2 diabetic patients. Biomarkers in medicine 2 34169731
2026 ADAMTS7 promotes smooth muscle foam cell expansion in atherosclerosis. The Journal of clinical investigation 1 41609669
2022 ADAMTS7 Attenuates House Dust Mite-Induced Airway Inflammation and Th2 Immune Responses. Lung 1 35503474
2020 Elevated serum cartilage oligomeric matrix protein and the metalloproteinase-ADAMTS7 levels are associated with vascular calcification in maintenance hemodialysis patients. Seminars in dialysis 1 32441044
2026 Genetic Variants and Molecular Components Associated with Metabolic Dysfunctional-Associated Steatotic Liver Disease and Depression: Shared Association of ADAMTS7 and THRAP3. Genes 0 41898876
2026 The biology and pathophysiology of the proatherogenic metalloprotease ADAMTS7. Open biology 0 41920022
2026 ADAMTS-7 Increase Contributes to Worsened Neurological Outcome in Mice on High Fat Diet. CNS neuroscience & therapeutics 0 41968389
2026 ADAMTS7 selective inhibitor BAY-9835 alleviates acute myocardial infarction by suppressing the NF-κB-mediated pyroptosis. Toxicology and applied pharmacology 0 42061659
2026 A functional polymorphism in ADAMTS7 3'-UTR abrogates miR-654-5p-mediated ADAMTS7 expression suppression and increases the incidence, short-term outcome, and recurrence of large artery atherosclerotic stroke among southern Chinese population. Artificial cells, nanomedicine, and biotechnology 0 42184821
2025 Direct Oral Anticoagulant-Related Bleeding in Atrial Fibrillation Patients Leads to ADAMTS7 Promoter Demethylation. Genes 0 40565590
2024 Circ_0104652 Promotes the Proliferation and Migration of ox-LDL-Stimulated Vascular Smooth Muscle Cells via Stabilizing ADAMTS7 and HMGB1. American journal of hypertension 0 38536049

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