| Autor: |
Smithies, Oliver, Bird, Kim E., Kakoki, Masao, Rojas, Mauricio, Suen, Alisa A., Lenhart, Kaitlin C., Li, Feng, Bai, Xue, Mack, Christopher P., Taylor, Joan M. |
| Jazyk: |
angličtina |
| Předmět: |
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| Popis: |
Although hypertension is a worldwide health issue, an incomplete understanding of its etiology has hindered our ability to treat this complex disease. Here we identify arhgap42 (also known as GRAF3) as a Rho-specific GAP expressed specifically in smooth muscle cells in mice and humans. We show that GRAF3-deficient mice exhibit significant hypertension and increased pressor responses to angiotensin II and endothelin-1; these effects are prevented by treatment with the Rho-kinase inhibitor, Y-27632. RhoA activity and myosin light chain phosphorylation are elevated in GRAF3-depleted smooth muscle cells in vitro and in vivo, and isolated vessel segments from GRAF3-deficient mice show increased contractility. Taken together our data indicate that GRAF3-mediated inhibition of RhoA activity in vascular smooth muscle cells is necessary for maintaining normal blood pressure homeostasis. Moreover, these findings provide a potential mechanism for a hypertensive locus recently identified within arhgap42 and provide a foundation for the future development of innovative hypertension therapies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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