Insulin resistance induces medial artery calcification in fructose-fed rats.
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.
The Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, Beijing 100029, China.
SourceExperimental biology and medicine (Maywood, N.J.) 237:1 2012 Jan pg 50-7
Bone Morphogenetic Proteins
Core Binding Factor Alpha 1 Subunit
Extracellular Matrix Proteins
Glucose Tolerance Test
Muscle, Smooth, Vascular
Sodium-Phosphate Cotransporter Proteins, Type III
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't