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.

Links

Publisher Full Text

Authors

Zhou YB, Zhang J, Cai Y, Teng X, Duan XH, Song JQ, Du J, Tang CS, Qi YF

Institution

The Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, Beijing 100029, China.

Source

Experimental biology and medicine (Maywood, N.J.) 237:1 2012 Jan 1 pg 50-7

MeSH

Alkaline Phosphatase
Animals
Aorta, Thoracic
Blood Glucose
Bone Morphogenetic Proteins
Calcium
Calcium-Binding Proteins
Cell Differentiation
Core Binding Factor Alpha 1 Subunit
Dietary Carbohydrates
Extracellular Matrix Proteins
Fructose
Glucose Tolerance Test
Insulin
Insulin Resistance
Lipid Peroxidation
Male
Muscle, Smooth, Vascular
Osteopontin
Osteoprotegerin
Phosphorus
RNA, Messenger
Random Allocation
Rats
Rats, Sprague-Dawley
Sodium-Phosphate Cotransporter Proteins, Type III
Tunica Media
Vascular Calcification

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22238287