Roles of Caveolin-1 in Angiotensin II–Induced Hypertrophy and Inward Remodeling of Cerebral Pial Arterioles
Angiotensin II (Ang II) is a major determinant of inward remodeling and hypertrophy in pial arterioles that may have an important role in stroke during chronic hypertension. Previously, we found that epidermal growth factor receptor is critical in Ang II–mediated hypertrophy that may involve caveolin-1 (Cav-1). In this study, we examined the effects of Cav-1 and matrix metalloproteinase-9 (MMP9) on Ang II–mediated structural changes in pial arterioles. Cav-1–deficient (Cav-1−/−), MMP9-deficient (MMP9−/−), and wild-type mice were infused with either Ang II (1000 ng/kg per minute) or saline via osmotic minipumps for 28 days (n=6–8 per group). Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of pial arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined histologically in pressurized fixed pial arterioles. Expression of Cav-1, MMP9, phosphorylated epidermal growth factor receptor, and Akt was determined by Western blotting and immunohistochemistry. Deficiency of Cav-1 or MMP9 did not affect Ang II–induced hypertension. Ang II increased the expression of Cav-1, phosphorylated epidermal growth factor receptor, and Akt in wild-type mice, which was attenuated in Cav-1−/− mice. Ang II–induced hypertrophy, inward remodeling, and increased MMP9 expression in pial arterioles were prevented in Cav-1−/− mice. Ang II–mediated increases in MMP9 expression and inward remodeling, but not hypertrophy, were prevented in MMP9−/− mice. In conclusion, Cav-1 is essential in Ang II–mediated inward remodeling and hypertrophy in pial arterioles. Cav-1–induced MMP9 is exclusively involved in inward remodeling, not hypertrophy. Further studies are needed to determine the role of Akt in Ang II–mediated hypertrophy.
- Received November 28, 2015.
- Revision received October 11, 2015.
- Accepted December 3, 2015.
- © 2016 American Heart Association, Inc.