Unbound MEDLINE

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.

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  • 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