A disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS7) is anenzyme that in humans is encoded by theADAMTS7 gene onchromosome 15.[1] It is ubiquitously expressed in many tissues and cell types.[2] This enzyme catalyzes the degradation ofcartilage oligomeric matrix protein (COMP).[3] ADAMTS7 has been associated withcancer andarthritis in multiple tissue types.[4][5] TheADAMTS7 gene also contains one of 27SNPs associated with increased risk ofcoronary artery disease.[6]
This 1686-amino acid protein belongs to theADAMTS family and is one of 19 members known in humans. As an ADAMTS protein, ADAMTS7 contains a sharedproteinasedomain and an ancillary domain. The proteinase domain can be further divided into asignal peptide, a prodomain, ametalloproteinase domain, and adisintegrin-like domain.[7] In particular, the metalloproteinase domain contains acysteine-switchmotif in itsbinding site for binding the catalyticzinc ion (Zn2+).[8] Apharmacophore model consisting of fourhydrogen bond donor sites and three hydrogen bond acceptor sites was proposed for this domain. Unlike the proteinase domain, the ancillary domain varies by ADAMTS protein and includes any number ofthrombospondin (TSP) type 1 motifs, one cysteine-rich and spacer domain, and other domains specific to certain ADAMTS proteins.[7] ADAMTS7 in particular possesses 8 TSP type 1 motifs which, together with its spacer domain, participate in the protein’stight interaction with theextracellular matrix.[8]
In vascularsmooth muscle cell (VSMC), ADAMTS7 mediatesVSMC migration, which plays an essential role during the development ofatherosclerosis andrestenosis.[9] Adamts7 deficiency in both the Ldlr−/− and Apoe−/− hyperlipidemic mouse models markedly attenuates formation of atherosclerotic lesions; furthermore, wire-injury experiments in the Adamts7−/− mouse show reducedneointima formation.[10] The association of ADAMTS7 with atherosclerosis suggests that inhibition of ADAMTS7 should be atheroprotective in humans.[10]
A negative correlation between the expression levels of specific miRNAs and ADAMTS7 is observed in normal tissues but not in disease tissues, implying an altered miRNA-target interaction in the disease state. Accordingly, expression profiles of these miRNAs and ADAMTS7 may be useful diagnostic tools to differentiate cancer and lichen planus from normal tissues.[11] ADAMTS7 has also been identified as a putative oncogene and reported to be mutated exclusively in Asians, which may have implications for the prevention and treatment of hepatocellular carcinoma.[4] In addition, ADAMTS7 plays a crucial role in the pathogenesis of arthritis.[5] For example, the FGF2/p65/miR-105/Runx2/ADAMTS axis is reportedly involved in osteoarthritis (OA) pathogenesis.[12] Specifically, ADAMTS7 forms apositive feedback loop with tumour necrosis factor (TNF)-α in the pathogenesis of OA.[13]
Genome-wide association studies identified ADAMTS7 as a risk locus for coronary artery disease. Studies have been carried on classification of ADAMTS7 binding site, which may serve as the first step toward developing a new therapeutic target for coronary artery disease.[7] Significant associations for coronary artery calcification with SNPs in ADAMTS7 has also been found in Hispanics.[14] Additionally, a multi-locus genetic risk score study based on a combination of 27 loci, including the ADAMTS7 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).[6]
^Wand, K.; Straub, M.; Lohmann, C. P.; Mayer, C. S. (2016-02-15). "[Sympathetic ophthalmia : Therapy with steroid-free immunosuppressant azathioprine]".Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft.113 (10):867–869.doi:10.1007/s00347-016-0227-7.ISSN1433-0423.PMID26879557.S2CID24394552.
