| First Author | Kanda T | Year | 2005 |
| Journal | Hypertension | Volume | 45 |
| Issue | 4 | Pages | 724-9 |
| PubMed ID | 15699465 | Mgi Jnum | J:110054 |
| Mgi Id | MGI:3630374 | Doi | 10.1161/01.HYP.0000153316.59262.79 |
| Citation | Kanda T, et al. (2005) Role of Rho-kinase and p27 in angiotensin II-induced vascular injury. Hypertension 45(4):724-9 |
| abstractText | Angiotensin II enhances the development of atherosclerotic lesion in which cellular proliferation and/or migration are critical steps. Although cyclin-dependent kinase inhibitor, p27, and Rho/Rho-kinase pathway have recently been implicated as factors regulating these events cooperatively, their role in vivo has not been fully elucidated. We evaluated the contribution of p27 and Rho-kinase to angiotensin II-induced vascular injury using p27-deficient mice. Two-week angiotensin II (1500 ng/kg per minute SC) infusion elicited similar degrees of elevation in systolic blood pressure in wild-type mice (159+/-5 mm Hg) and p27-deficient mice (157+/-5 mm Hg; P>0.05). Angiotensin II infusion to wild-type mice resulted in increases in the medial thickness of aorta, proliferating cell number, and monocyte/macrophage infiltration within the vasculature. In p27-deficient mice, however, these changes were more prominent than those in wild-type mice. Treatment of wild-type mice with fasudil, a selective Rho-kinase inhibitor, did not alter blood pressure but significantly upregulated p27 expression, decreased medial thickness of aorta, reduced proliferating cell number, and prevented monocyte/macrophage infiltration. These protective effects of fasudil were attenuated in p27-deficient mice. In conclusion, p27 constitutes an important modulator of angiotensin II-induced monocyte/macrophage infiltration and vascular remodeling, which is mediated in part by Rho-kinase stimulation. Inhibition of Rho-kinase activity improves angiotensin II-induced vascular injury through p27-dependent and p27-independent mechanisms. |
