Endothelial dysfunction in Type 2 diabetes correlates with deregulated expression of the tail-anchored membrane protein SLMAP

被引:19
作者
Ding, H
Howarth, AG
Pannirselvam, M
Anderson, TJ
Severson, DL
Wiehler, WB
Triggle, CR
Tuana, BS
机构
[1] RMIT Univ, Sch Med Sci, Bundoora, Vic 3083, Australia
[2] Univ Toronto, Dept Med, Toronto, ON, Canada
[3] Univ Ottawa, Fac Med, Dept Cellular & Mol Med, Ottawa, ON, Canada
[4] Univ Calgary, Fac Med, Smooth Muscle Res Grp, Calgary, AB, Canada
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2005年 / 289卷 / 01期
关键词
mice; microvascular function; gene expression; sarcolemmal membrane-associated protein;
D O I
10.1152/ajpheart.00037.2005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The Type 2 diabetic db/db mouse experiences vascular dysfunction typified by changes in the contraction and relaxation profiles of small mesenteric arteries (SMAs). Contractions of SMAs from the db/db mouse to the alpha(1)-adrenoceptor agonist phenylephrine (PE) were significantly enhanced, and acetylcholine (ACh)-induced relaxations were significantly depressed. Drug treatment of db/db mice with a nonthiazolidinedione peroxisome prolifetor-activated receptor-gamma agonist and insulin sensitizing agent 2-[2-(4-phenoxy-2-propylphenoxy)ethyl]indole-5-acetic acid (COOH) completely prevented the changes in endothelium-dependent relaxation, but, with the discontinuation of therapy, endothelial dysfunction returned. Dysfunctional SMAs were found to specifically upregulate the expression of a 35-kDa isoform of sarcolemmal membrane-associated protein (SLMAP), which is a component of the excitation-contraction coupling apparatus and implicated in the regulation of membrane function in muscle cells. Real-time PCR revealed high SLMAP mRNA levels in the db/db microvasculature, which were markedly downregulated during COOH treatment but elevated again when drug therapy was discontinued. These data reveal that the microvasculature in db/db mice undergoes significant changes in vascular function with the endothelial component of vascular dysfunction specifically correlating with the overexpression of SLMAP. Thus changes in SLMAP expression may be an important indicator for microvascular disease associated with Type 2 diabetes.
引用
收藏
页码:H206 / H211
页数:6
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