| First Author | Pushpakumar S | Year | 2013 |
| Journal | J Hypertens | Volume | 31 |
| Issue | 11 | Pages | 2270-81; discussion 2281 |
| PubMed ID | 24077247 | Mgi Jnum | J:280603 |
| Mgi Id | MGI:6367487 | Doi | 10.1097/HJH.0b013e3283649b33 |
| Citation | Pushpakumar S, et al. (2013) Angiotensin-II induced hypertension and renovascular remodelling in tissue inhibitor of metalloproteinase 2 knockout mice. J Hypertens 31(11):2270-81; discussion 2281 |
| abstractText | BACKGROUND: Sustained hypertension induces renovascular remodelling by altering extracellular matrix (ECM) components. Matrix metalloproteinases (MMPs) are Zn-dependent enzymes that regulate ECM turnover in concert with their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). Increased MMP-2 and MMP-9 have been implicated in hypertensive complications; however, the contribution of individual MMPs/TIMPs in renal remodelling has not been fully elucidated. The purpose of this study was to determine the effect of TIMP2 deficiency and thus MMP-2 on angiotensin-II (Ang-II) induced renal remodelling. METHOD: C57BL/6J (wild-type) and TIMP2 knockout mice were infused with Ang-II at 250 ng/kg per min for 4 weeks. Blood pressure was measured weekly and end-point laser Doppler flowmetry was done to assess cortical blood flow. Immunohistochemical staining was performed for collagen and elastin analyses. The activity of MMP-9 and MMP-2 was determined by Gelatin zymography. RESULTS: Ang-II induced similar elevation in mean blood pressure in TIMP2 and wild-type mice. In TIMP2 mice, Ang-II treatment was associated with a greater reduction in renal cortical blood flow and barium angiography demonstrated decreased vascular density compared with Ang-II treated wild-type mice. Peri-glomerular and vascular collagen deposition was increased and elastin content was decreased causing increased wall-to-lumen ratio in TIMP2 mice compared with wild-type mice receiving Ang-II. Ang-II increased the expression and activity of MMP-9 predominantly in TIMP2 mice than in wild-type mice. CONCLUSION: These results suggest that TIMP2 deficiency exacerbates renovascular remodelling in agonist-induced hypertension by a mechanism that may, in part, be attributed to increased activity of MMP-9. |
