JCAD/KIAA1462, a coronary artery disease-associated gene product, regulates endothelial function

ABSTRACT: Recent genome-wide association studies (GWAS) have identified gene variants associated with coronary artery disease including ADAMTS7, PHACTR1, KIAA1462/JCAD (Junctional Protein Associated with Coronary Artery Disease) and many others. JCAD has been identified as a novel component of endothelial cell-cell junctions (Akashi et al., 2011, BBRC) and regulates angiogenesis (Hara et al, ATVB, 2017). In our study, we observed that JCAD is a 148-KDa protein identified by mass spectrometry, but display a band shift to around 180-200 KDa, suggesting that JCAD is subject to multiple post-translatinonal modification. We also observed that JCAD well colocalized with adheren junction VE-cadherin, tight junction ZO-1 and desmosome junction plakoglobin (also known as gamma-catenin). However, the functional role of JCAD in endothelial function and the etiology of vascular disease remains unknown. In view of the critical role of junctional proteins in regulating endothelial function including vascular permeability, angiogenesis, and monocyte adhesion, we hypothesized that JCAD may play a crucial role in regulating endothelial function. To better understand the function of JCAD in endothelial cells, we performed RNA-sequencing based transcriptomic profiling in JCAD depleted (by transfection with by JCAD siRNA) human coronary artery endothelial cells, to identify critical genes and pathways associated with JCAD. We found that multiple atherosclerosis related genes and pathways are modulated by JCAD. Further studies are needed to characterize the biological function of JCAD in the pathogenesis of cardiometabolic diseases associated with endothelial dysfunction, such as diabetes, obesity, hypertension and atherosclerosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE102498 | GEO | 2018/08/10

REPOSITORIES: GEO