Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: relation to vessel size.

Hdl Handle:
http://hdl.handle.net/10675.2/77
Title:
Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: relation to vessel size.
Authors:
Song, WeiWei; Ergul, Adviye
Abstract:
BACKGROUND: Hyperglycemia-induced changes in vascular wall structure contribute to the pathogenesis of diabetic microvascular and macrovascular complications. Matrix metalloproteinases (MMP), a family of proteolytic enzymes that degrade extracellular matrix (ECM) proteins, are essential for vascular remodeling. We have shown that endothelin-1 (ET-1) mediates increased MMP activity and associated vascular remodeling in Type 2 diabetes. However, the effect of Type 2 diabetes and/or ET-1 on the regulation of ECM and MMP gene expression in different vascular beds remains unknown. METHODS: Aorta and mesenteric artery samples were isolated from control, Type 2 diabetic Goto-Kakizaki (GK) rats and GK rats treated with ETA antagonist ABT-627. Gene expression profile of MMP-2, MMP-9, MT1-MMP, fibronectin, procollagen type 1, c-fos and c-jun, were determined by quantitative real-time (qRT) PCR. In addition, aortic gene expression profile was evaluated by an ECM & Adhesion Molecules pathway specific microarray approach. RESULTS: Analysis of the qRT-PCR data demonstrated a significant increase in mRNA levels of MMPs and ECM proteins as compared to control animals after 6 weeks of mild diabetes. Furthermore, these changes were comparable in aorta and mesentery samples. In contrast, treatment with ETA antagonist prevented diabetes-induced changes in expression of MMPs and procollagen type 1 in mesenteric arteries but not in aorta. Microarray analysis provided evidence that 27 extracellular matrix genes were differentially regulated in diabetes. Further qRT-PCR with selected 7 genes confirmed the microarray data. CONCLUSION: These results suggest that the expression of both matrix scaffold protein and matrix degrading MMP genes are altered in macro and microvascular beds in Type 2 diabetes. ETA antagonism restores the changes in gene expression in the mesenteric bed but not in aorta suggesting that ET-1 differentially regulates microvascular gene expression in Type 2 diabetes.
Citation:
Cardiovasc Diabetol. 2006 Feb 17; 5:3
Issue Date:
10-Apr-2006
URI:
http://hdl.handle.net/10675.2/77
DOI:
10.1186/1475-2840-5-3
PubMed ID:
16503991
PubMed Central ID:
PMC1434726
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
ISSN:
1475-2840
Appears in Collections:
Vascular Biology Center: Faculty Research and Publication

Full metadata record

DC FieldValue Language
dc.contributor.authorSong, WeiWeien_US
dc.contributor.authorErgul, Adviyeen_US
dc.date.accessioned2010-09-24T21:44:44Z-
dc.date.available2010-09-24T21:44:44Z-
dc.date.issued2006-04-10en_US
dc.identifier.citationCardiovasc Diabetol. 2006 Feb 17; 5:3en_US
dc.identifier.issn1475-2840en_US
dc.identifier.pmid16503991en_US
dc.identifier.doi10.1186/1475-2840-5-3en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/77-
dc.description.abstractBACKGROUND: Hyperglycemia-induced changes in vascular wall structure contribute to the pathogenesis of diabetic microvascular and macrovascular complications. Matrix metalloproteinases (MMP), a family of proteolytic enzymes that degrade extracellular matrix (ECM) proteins, are essential for vascular remodeling. We have shown that endothelin-1 (ET-1) mediates increased MMP activity and associated vascular remodeling in Type 2 diabetes. However, the effect of Type 2 diabetes and/or ET-1 on the regulation of ECM and MMP gene expression in different vascular beds remains unknown. METHODS: Aorta and mesenteric artery samples were isolated from control, Type 2 diabetic Goto-Kakizaki (GK) rats and GK rats treated with ETA antagonist ABT-627. Gene expression profile of MMP-2, MMP-9, MT1-MMP, fibronectin, procollagen type 1, c-fos and c-jun, were determined by quantitative real-time (qRT) PCR. In addition, aortic gene expression profile was evaluated by an ECM & Adhesion Molecules pathway specific microarray approach. RESULTS: Analysis of the qRT-PCR data demonstrated a significant increase in mRNA levels of MMPs and ECM proteins as compared to control animals after 6 weeks of mild diabetes. Furthermore, these changes were comparable in aorta and mesentery samples. In contrast, treatment with ETA antagonist prevented diabetes-induced changes in expression of MMPs and procollagen type 1 in mesenteric arteries but not in aorta. Microarray analysis provided evidence that 27 extracellular matrix genes were differentially regulated in diabetes. Further qRT-PCR with selected 7 genes confirmed the microarray data. CONCLUSION: These results suggest that the expression of both matrix scaffold protein and matrix degrading MMP genes are altered in macro and microvascular beds in Type 2 diabetes. ETA antagonism restores the changes in gene expression in the mesenteric bed but not in aorta suggesting that ET-1 differentially regulates microvascular gene expression in Type 2 diabetes.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshAorta / drug effects / physiology / physiopathologyen_US
dc.subject.meshBlood Vessels / physiopathologyen_US
dc.subject.meshDiabetes Mellitus, Type 2 / genetics / physiopathologyen_US
dc.subject.meshEndothelin-1 / pharmacologyen_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshHyperglycemia / complicationsen_US
dc.subject.meshMaleen_US
dc.subject.meshMatrix Metalloproteinases / drug effects / geneticsen_US
dc.subject.meshMesenteric Arteries / drug effects / physiology / physiopathologyen_US
dc.subject.meshOligonucleotide Array Sequence Analysisen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshPyrrolidines / pharmacologyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Wistaren_US
dc.subject.meshReceptors, Endothelin / antagonists & inhibitorsen_US
dc.subject.meshReference Valuesen_US
dc.titleType-2 diabetes-induced changes in vascular extracellular matrix gene expression: relation to vessel size.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, N.I.H., Extramuralen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC1434726en_US
dc.contributor.corporatenameVascular Biology Centeren_US

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