title: Diabetes and arterial extracellular matrix changes in a porcine model of atherosclerosis.
abstract: 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.affiliation: Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA 98195-6422, USA.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: McDonald
authors.forename: Ross G
authors.initials: RG
authors.lastname: Gerrity
authors.forename: Christy
authors.initials: C
authors.lastname: Jen
authors.forename: Hao-Ji
authors.initials: HJ
authors.lastname: Chen
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wark
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
authors.forename: Alan
authors.initials: A
authors.lastname: Chait
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D058578:Biglycan; D003324:Coronary Artery Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D006949:Hyperlipidemias / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D011509:Proteoglycans / Q000378:metabolism; D013552:Swine; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D053675:Versicans / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D053675:Versicans; D006820:Hyaluronic Acid; D004549:Elastin