{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T08:08:05Z","timestamp":1780301285021,"version":"3.54.0"},"reference-count":32,"publisher":"The Company of Biologists","issue":"5","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":31,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82170300"],"award-info":[{"award-number":["82170300"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31970509"],"award-info":[{"award-number":["31970509"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["GZC20241712"],"award-info":[{"award-number":["GZC20241712"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>ADAMTS5 is an enzyme that cleaves chondroitin sulfate proteoglycans such as versican (VCAN) and aggrecan (ACAN). The Adamts5\u2212\/\u2212 mouse model exhibits aortic anomalies, and increased expression of Adamts4 and Adamts5 leads to excessive versican degradation and reduced cardiac jelly. In zebrafish, knockdown of adamts5 rescues the cardiac phenotype conferred by ccm1 deficiency in zebrafish embryos. Here, we generated an ADAMTS5 knockin mouse model (ADAMTS5KI) to characterize the effect of induced expression of human ADAMTS5 on the cardiovascular system in mice. Sustained expression of ADAMTS5 in the endothelium diminished cardiac jelly formation and proteoglycan deposition in the atrioventricular cushion, and led to cardiac development arrest. Induced expression of ADAMTS5 in the endothelium of postnatal mice impaired cardiac valve patterning. Expression of ADAMTS5 in brain endothelial cells did not confer an obvious vascular defect. However, expression of ADAMTS5 in brain endothelial cells of Ccm2-deficient mice aggravated cerebral cavernous malformation (CCM) lesion burden and shortened the life span of Ccm2-deficient mice. These findings suggest that tight regulation of ADAMTS5 in the endothelium is essential for cardiovascular development and structural integrity, and that ADAMTS5 interacts with CCM signaling, contributing to CCM disease progression.<\/jats:p>","DOI":"10.1242\/dmm.052668","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T07:01:37Z","timestamp":1779087697000},"source":"Crossref","is-referenced-by-count":0,"title":["Knockin expression of human ADAMTS5 impairs cardiovascular development and aggravates cerebral cavernous malformations in mice"],"prefix":"10.1242","volume":"19","author":[{"given":"Xi","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Zoology, Chinese Academy of Sciences 1 State Key Laboratory of Organ Regeneration and Reconstruction , , Beijing 100101 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Medical University 2 Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, and Center for Cardiovascular Diseases , , Tianjin 300070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-9030","authenticated-orcid":false,"given":"Zifeng","family":"Dai","sequence":"additional","affiliation":[{"name":"Tianjin Medical University 2 Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, and Center for Cardiovascular Diseases , , Tianjin 300070 ,","place":["China"]},{"name":"The First Affiliated Hospital of Ningbo University 3 Neurosurgery Department , , Ningbo 315010 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzi","family":"Yang","sequence":"additional","affiliation":[{"name":"Tianjin Medical University 2 Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, and Center for Cardiovascular Diseases , , Tianjin 300070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6906-3804","authenticated-orcid":false,"given":"Liya","family":"Xie","sequence":"additional","affiliation":[{"name":"Tianjin Medical University 2 Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, and Center for Cardiovascular Diseases , , Tianjin 300070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Zoology, Chinese Academy of Sciences 1 State Key Laboratory of Organ Regeneration and Reconstruction , , Beijing 100101 ,","place":["China"]},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine 4 , Beijing 100101 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjian","family":"Zheng","sequence":"additional","affiliation":[{"name":"Tianjin Medical University 2 Department of Pharmacology and Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, and Center for Cardiovascular Diseases , , Tianjin 300070 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-1236","authenticated-orcid":false,"given":"Zhiming","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Zoology, Chinese Academy of Sciences 1 State Key Laboratory of Organ Regeneration and Reconstruction , , Beijing 100101 ,","place":["China"]},{"name":"Beijing Institute for Stem Cell and Regenerative Medicine 4 , Beijing 100101 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"2026060103533065200_DMM052668C1","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1161\/CIRCULATIONAHA.121.055732","article-title":"Extracellular matrix in heart failure: role of ADAMTS5 in proteoglycan remodeling","volume":"144","author":"Barallobre-Barreiro","year":"2021","journal-title":"Circulation"},{"key":"2026060103533065200_DMM052668C2","doi-asserted-by":"publisher","first-page":"e97167","DOI":"10.1172\/jci.insight.97167","article-title":"Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection","volume":"3","author":"Cikach","year":"2018","journal-title":"JCI Insight"},{"key":"2026060103533065200_DMM052668C3","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.joca.2021.08.012","article-title":"Pharmacological characterization of GLPG1972\/S201086, a potent and 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