title: Insulin resistance induces medial artery calcification in fructose-fed rats.
abstract: Osteogenic differentiation of vascular smooth muscle cells (VSMCs) results in medial artery calcification, which is common in diabetes, but the pathogenesis is poorly understood. We aimed to explore the pathophysiological roles of insulin resistance (IR) on medial artery calcification in rats with 10% fructose in drinking water. After 12 weeks of fructose feeding, rats showed severe IR, with increased levels of fasting blood glucose, serum insulin and oral glucose tolerance test (OGTT). Fructose-fed rats showed aortic calcification, increased aortic calcium deposition and irregular elastic fibers in the medial layer of the vessel wall. Moreover, plasma phosphorus concentration, calcium × phosphorus product and alkaline phosphatase (ALP) activity, and aortic calcium content and ALP activity were significantly increased. Fructose feeding increased mRNA levels of osteopontin, type III sodium-dependent phosphate co-transporter, bone morphogenetic protein-2 and the key transcription factor core binding factor alpha 1 in aortic tissue and downregulated mRNA levels of osteoprotegerin and matrix γ-carboxyglutamic acid protein. Fructose feeding decreased protein levels of smooth-muscle lineage markers and induced severe lipid peroxidation injury. IR induced by high fructose feeding could evoke osteogenic transdifferentiation of VSMCs and promote vascular calcification.
authors.affiliation: The Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, Beijing 100029, China.
authors.forename: Ye-bo
authors.initials: YB
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Xu
authors.initials: X
authors.lastname: Teng
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Duan
authors.forename: Jun-qiu
authors.initials: JQ
authors.lastname: Song
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.forename: Chao-shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Yong-fen
authors.initials: YF
authors.lastname: Qi
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology*; D001786:Blood Glucose / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics; D002118:Calcium / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D002454:Cell Differentiation; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005632:Fructose / Q000008:administration & dosage*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015227:Lipid Peroxidation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D053495:Osteopontin / Q000096:biosynthesis / Q000235:genetics; D053244:Osteoprotegerin / Q000096:biosynthesis; D010758:Phosphorus / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000096:biosynthesis / Q000235:genetics; D017540:Tunica Media / Q000473:pathology; D061205:Vascular Calcification / Q000473:pathology* / Q000503:physiopathology*; D000097568:Matrix Gla Protein
chemical_list: D000469:Alkaline Phosphatase; D001786:Blood Glucose; D019485:Bone Morphogenetic Proteins; D002118:Calcium; D002135:Calcium-Binding Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D004040:Dietary Carbohydrates; D016326:Extracellular Matrix Proteins; D005632:Fructose; D007328:Insulin; D053495:Osteopontin; D053244:Osteoprotegerin; D010758:Phosphorus; D012333:RNA, Messenger; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D000097568:Matrix Gla Protein