Document Detail


Diabetes and arterial extracellular matrix changes in a porcine model of atherosclerosis.
MedLine Citation:
PMID:  17652266     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients with diabetes are at substantially increased risk for atherosclerosis and clinical cardiovascular events. Because arterial extracellular matrix contains several molecules, including biglycan, versican, hyaluronan, and elastin, that may affect plaque lipid retention and stability, we determined whether diabetes affects plaque content of these molecules in a porcine model of hyperlipidemia and diabetes. Coronary artery sections were studied from non-diabetic normolipidemic (n=11, N-NL), diabetic normolipidemic (n=10, DM-NL), non-diabetic hyperlipidemic (n=16, N-HL), and diabetic hyperlipidemic (n=15, DM-HL) animals. Hyaluronan, biglycan, versican, and apolipoprotein B (apoB) were detected with monospecific peptides or antisera, and elastin with Movat's pentachrome stain, and contents of each were quantified by computer-assisted morphometry. In the hyperlipidemic groups, diabetes was associated with a 4-fold increase in intimal area, with strong correlations between intimal area and immunostained areas for hyaluronan (R(2) = 0.83, p<0.0001), biglycan (R(2) = 0.72, p<0.0001), and apoB (R(2) = 0.23, p=0.0069). In contrast, median (interquartile range) intimal elastin content was significantly lower with diabetes [N-HL: 5.2% (2.4-8.2%) vs DM-HL: 1.5% (0.5-4.2%), p=0.01], and there was a strong negative correlation between intimal total and elastin areas (Spearman r = -0.62, p=0.001). In this porcine model, diabetes was associated with multiple extracellular matrix changes that have been associated with increased lesion instability, greater atherogenic lipoprotein retention, and accelerated atherogenesis.
Authors:
Thomas O McDonald; Ross G Gerrity; Christy Jen; Hao-Ji Chen; Kathleen Wark; Thomas N Wight; Alan Chait; Kevin D O'Brien
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-07-24
Journal Detail:
Title:  The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society     Volume:  55     ISSN:  0022-1554     ISO Abbreviation:  J. Histochem. Cytochem.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-22     Completed Date:  2007-11-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9815334     Medline TA:  J Histochem Cytochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1149-57     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA 98195-6422, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoproteins B / metabolism
Coronary Artery Disease / etiology,  metabolism,  pathology*
Coronary Vessels / metabolism,  pathology*
Diabetes Mellitus, Experimental / complications,  metabolism,  pathology*
Elastin / metabolism
Extracellular Matrix / metabolism,  pathology*
Extracellular Matrix Proteins / metabolism
Hyaluronic Acid / metabolism
Hyperlipidemias / complications,  metabolism,  pathology*
Lipoproteins, LDL / metabolism
Male
Proteoglycans / metabolism
Swine
Tunica Intima / metabolism,  pathology
Versicans / metabolism
Grant Support
ID/Acronym/Agency:
DK-02456/DK/NIDDK NIH HHS; HL-55798/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins B; 0/Extracellular Matrix Proteins; 0/Lipoproteins, LDL; 0/Proteoglycans; 123939-84-4/biglycan; 126968-45-4/Versicans; 9004-61-9/Hyaluronic Acid; 9007-58-3/Elastin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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