Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel size
<p>Abstract</p> <p>Background</p> <p>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 extracel...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2006-02-01
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| Series: | Cardiovascular Diabetology |
| Online Access: | http://www.cardiab.com/content/5/1/3 |
| _version_ | 1819122807234101248 |
|---|---|
| author | Ergul Adviye Song WeiWei |
| author_facet | Ergul Adviye Song WeiWei |
| author_sort | Ergul Adviye |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>Aorta and mesenteric artery samples were isolated from control, Type 2 diabetic Goto-Kakizaki (GK) rats and GK rats treated with ET<sub>A </sub>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.</p> <p>Results</p> <p>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. Futhermore, these changes were comparable in aorta and mesentery samples. In contrast, treatment with ET<sub>A </sub>antagonist prevented diabetes-induced changes in expression of MMPs and procollagen type 1 in mesenteric arteries but not in aorta. Microaarray analysis provided evidence that 27 extracellular matrix genes were differentially regulated in diabetes. Further qRT-PCR with selected 7 genes confirmed the microarray data.</p> <p>Conclusion</p> <p>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. ET<sub>A </sub>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.</p> |
| first_indexed | 2024-12-22T06:58:19Z |
| format | Article |
| id | doaj.art-bc9fba8aa9954d12a9a49b7a288e6426 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-12-22T06:58:19Z |
| publishDate | 2006-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-bc9fba8aa9954d12a9a49b7a288e64262022-12-21T18:34:52ZengBMCCardiovascular Diabetology1475-28402006-02-0151310.1186/1475-2840-5-3Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel sizeErgul AdviyeSong WeiWei<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>Aorta and mesenteric artery samples were isolated from control, Type 2 diabetic Goto-Kakizaki (GK) rats and GK rats treated with ET<sub>A </sub>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.</p> <p>Results</p> <p>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. Futhermore, these changes were comparable in aorta and mesentery samples. In contrast, treatment with ET<sub>A </sub>antagonist prevented diabetes-induced changes in expression of MMPs and procollagen type 1 in mesenteric arteries but not in aorta. Microaarray analysis provided evidence that 27 extracellular matrix genes were differentially regulated in diabetes. Further qRT-PCR with selected 7 genes confirmed the microarray data.</p> <p>Conclusion</p> <p>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. ET<sub>A </sub>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.</p>http://www.cardiab.com/content/5/1/3 |
| spellingShingle | Ergul Adviye Song WeiWei Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel size Cardiovascular Diabetology |
| title | Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel size |
| title_full | Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel size |
| title_fullStr | Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel size |
| title_full_unstemmed | Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel size |
| title_short | Type-2 diabetes-induced changes in vascular extracellular matrix gene expression: Relation to vessel size |
| title_sort | type 2 diabetes induced changes in vascular extracellular matrix gene expression relation to vessel size |
| url | http://www.cardiab.com/content/5/1/3 |
| work_keys_str_mv | AT erguladviye type2diabetesinducedchangesinvascularextracellularmatrixgeneexpressionrelationtovesselsize AT songweiwei type2diabetesinducedchangesinvascularextracellularmatrixgeneexpressionrelationtovesselsize |