title: Endoplasmic Reticulum Stress-Mediated Apoptosis Contributing to High Glucose-Induced Vascular Smooth Muscle Cell Calcification.
abstract: Vascular calcification (VC) is a common feature in patients with type 2 diabetes mellitus, a metabolic disorder that is characterized by hyperglycemia (high blood glucose) in the context of insulin resistance and a relative lack of insulin. Recently, a few studies have indicated that a high concentration of glucose amplifies the osteogenesis of vascular smooth muscle cells (VSMCs). Some previous reports state that endoplasmic reticulum (ER) stress-mediated apoptosis was activated in and contributed to VC. However, whether or not high glucose could induce ER stress-mediated apoptosis and then involve the pathogenesis of VC remains unclear. The purpose of the present study was to investigate whether high blood glucose-induced VC in diabetes mellitus is caused by the ER response and subsequent apoptosis. We examined the effects of high glucose on the ER stress response of VSMCs. High glucose treatment drastically increased the ER stress response in VSMCs. The high glucose-induced osteoblastic differentiation of VSMCs was significantly attenuated by pretreatment with 500 μM of 4-PBA (an ER stress inhibitor) prior to the exposure to high glucose, as evidenced by decreases in the expression of Runx2 and activity of alkaline phosphatase, as well as calcium nodules. These results suggest that high glucose induces the ER stress response and apoptosis, leading to high glucose-elicited VC.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhu
authors.forename: Runmin
authors.initials: R
authors.lastname: Guo
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Duguan
authors.initials: D
authors.lastname: Fu
authors.forename: Fuyuan
authors.initials: F
authors.lastname: Liu
authors.forename: Jiefen
authors.initials: J
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005947:Glucose / Q000633:toxicity*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D010654:Phenylbutyrates / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D061205:Vascular Calcification / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D010654:Phenylbutyrates; C493717:Runx2 protein, rat; C075773:4-phenylbutyric acid; D000469:Alkaline Phosphatase; D005947:Glucose