| First Author | Bai X | Year | 2013 |
| Journal | Nat Commun | Volume | 4 |
| Pages | 2910 | PubMed ID | 24335996 |
| Mgi Jnum | J:221301 | Mgi Id | MGI:5638847 |
| Doi | 10.1038/ncomms3910 | Citation | Bai X, et al. (2013) The smooth muscle-selective RhoGAP GRAF3 is a critical regulator of vascular tone and hypertension. Nat Commun 4:2910 |
| abstractText | Although hypertension is a worldwide health issue, an incomplete understanding of its aetiology 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 (SMCs) 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, Y27632. RhoA activity and myosin light chain phosphorylation are elevated in GRAF3-depleted SMCs 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 SMCs is necessary for maintaining normal blood pressure homoeostasis. 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. |
