{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have identified JCAD (junctional cadherin 5 associated; formerly known as KIAA1462) as an important endothelial cell–cell junction protein implicated in coronary artery disease. Genome‐wide association analyses have linked risk alleles at the JCAD locus to increased gene expression in human arteries and a higher prevalence of myocardial infarction, suggesting a causal role in vascular pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In functional studies, JCAD localizes specifically to VE‐cadherin–based cell–cell junctions in endothelial cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", where it regulates key endothelial phenotypes such as proliferation, migration, apoptosis, tube formation, and monocyte adhesion. Mechanistically, JCAD interacts with components of the Hippo signaling cascade—most notably binding to LATS2 and actin‐binding partners like TRIOBP—to negatively regulate Hippo pathway activity. This suppression leads to enhanced nuclear activity of the YAP/TAZ transcriptional co-activators and the subsequent upregulation of pro-atherogenic genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Consistent with these findings, experimental loss of JCAD in animal models improves endothelium-dependent relaxation and reduces high fat diet–induced atherosclerosis. Collectively, these data suggest that JCAD plays a central role in coupling endothelial junction integrity and mechanotransduction with Hippo signaling, thereby contributing to vascular dysfunction and the development of atherosclerotic lesions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Suowen Xu, Yanni Xu, Peng Liu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A coronary artery disease-associated gene product, JCAD/KIAA1462, is a novel component of endothelial cell-cell junctions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2011.08.073"}], "href": "https://doi.org/10.1016/j.bbrc.2011.08.073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21884682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21884682"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Peter D Jones, Michael A Kaiser, Maryam Ghaderi Najafabadi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A key role for the novel coronary artery disease gene JCAD in atherosclerosis via shear stress mechanotransduction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvz263"}], "href": "https://doi.org/10.1093/cvr/cvz263"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31584065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31584065"}]}]}]}