title: Down regulation of Jag-1 in VSMCs contributes to impaired angiogenesis under high glucose condition: Experimental study using aortic rings of rats.
abstract: The major cause of diabetes-related mortality is the complications involving aberrant angiogenesis. To understand the underlying mechanisms of such altered-angiogenesis in diabetes, examining the interaction between endothelial cells (ECs) and neighboring smooth muscle cells (VSMCs) rather than mainly focusing on EC might provide us useful information. Thus, in the present study, we examined the effect of high glucose on the expression of Jag1, one of the key trans-activating ligands of Notch receptors known to be involved in EC-SMC interaction, as well as angiogenic process, in vascular smooth muscle cells (VSMCs) to elucidate possible role of EC-VSMC interaction in diabetes-related angiopathy. Our data indicate that high glucose condition decreases the expression of Jag1 in VSMCs possibly by increasing Jag1-targeting micro RNAs (miRNAs) such as miR-21, and exogenous Jag1-simulating peptides increase proliferation and migration of ECs under high glucose condition in vitro. Ex vivo study using aortic rings from normal and streptozotocin (STZ)-treated diabetic mouse demonstrated that exogenous Jag1-simulating peptides increases EC sprouting of aortic rings from diabetic mouse under high glucose condition. Our data suggest that EC-VSMC interaction is altered under high glucose condition and restoring EC-VSMC interaction can be a feasible therapeutic target for treating diabetes-related angiopathy.
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Korea.|Catholic Kwandong University International St. Mary's Hospital, Incheon Metropolitan City, Korea.
authors.forename: Seahyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Cardiology, The Fourth Hospital of Harbin Medical University, China.
authors.forename: Long-Hao
authors.initials: LH
authors.lastname: Yu
authors.affiliation: Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: La-Ri
authors.initials: LR
authors.lastname: Lim
authors.affiliation: Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Si
authors.affiliation: Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.|Division of Cardiology, Yonsei University Health System, Seoul, Korea.
authors.forename: Young-Guk
authors.initials: YG
authors.lastname: Ko
authors.affiliation: Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, Korea.|Catholic Kwandong University International St. Mary's Hospital, Incheon Metropolitan City, Korea.
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology*; D001786:Blood Glucose; D049109:Cell Proliferation; D002478:Cells, Cultured; D048909:Diabetes Complications / Q000097:blood*; D015536:Down-Regulation; D000072100:Jagged-1 Protein / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009389:Neovascularization, Pathologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D001786:Blood Glucose; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein
keywords: Angiogenesis; High glucose; Jag-1; aortic ring assay; miR-21; vascular smooth muscle cell