Matrix metalloproteinase-2 activity, protein, mRNA, and tissue inhibitors in small arteries from pregnant and relaxin-treated nonpregnant rats
| Autor: | Kirk P. Conrad, Laurie J. Kerchner, Michelle C. Fisher, Ketah D. Doty, Jonathan T. McGuane, Arundhathi Jeyabalan |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Physiology Biology Matrix metalloproteinase Renal vasodilation Pregnancy Physiology (medical) Internal medicine medicine Gelatinase Animals RNA Messenger Relaxin Messenger RNA Tissue Inhibitor of Metalloproteinase-2 Tissue Inhibitor of Metalloproteinase-1 Mechanism (biology) Reverse Transcriptase Polymerase Chain Reaction Tissue Inhibitor of Metalloproteinases Arteries medicine.disease Mesenteric Arteries Rats Enzyme Activation Vasodilation Endocrinology Matrix Metalloproteinase 2 Pregnancy Animal Female Endothelium Vascular |
| Zdroj: | Journal of applied physiology (Bethesda, Md. : 1985). 100(6) |
| ISSN: | 8750-7587 |
| Popis: | Vascular gelatinase activity is essential for pregnancy- and relaxin (Rlx)-induced renal vasodilation and hyperfiltration in rats. The objective of this study was to further elucidate the mechanisms for the increase in vascular matrix metalloproteinase (MMP)-2 activity caused by pregnancy and Rlx. We first corroborated our earlier work by showing that pro- and active forms of MMP-2 were increased in small renal arteries from pregnant compared with virgin rats and Rlx-treated compared with vehicle-treated nonpregnant rats. We next investigated other artery types and showed that MMP-2 activity was upregulated in mesenteric arteries from pregnant rats (pro-MMP-2 by 50% and active MMP-2 by 40%, both P < 0.05) and from Rlx-treated nonpregnant rats (pro-MMP-2 by 50% and active MMP-2 by 90%, both P < 0.005) compared with their respective controls. To corroborate these results obtained by gelatin zymography, pro-MMP-2 protein was determined by Western analysis in the same small arteries. Pro-MMP-2 protein was increased in small renal arteries from pregnant compared with virgin rats and from Rlx- compared with vehicle-treated nonpregnant rats: pro-MMP-2-to-β-actin ratio = 0.29 vs. 0.21 ( P < 0.01) and 0.43 vs. 0.32 ( P < 0.005). Findings were similar for mesenteric arteries. MMP-2 mRNA as measured by real-time PCR was increased in small renal arteries from pregnant and Rlx-treated nonpregnant rats compared with their respective controls. There were no significant differences in tissue inhibitor of metalloproteinase (TIMP-1 or TIMP-2) activity by reverse zymography in small renal arteries. Thus increases in MMP-2 mRNA and protein expression are major factors contributing to increased MMP-2 activity in small arteries from pregnant and Rlx-treated nonpregnant rats. |
| Databáze: | OpenAIRE |
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