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Increased Expression and Activity of RhoA Are Associated
With Increased DNA Synthesis and Reduced p27Kip1
Expression in the Vasculature of Hypertensive Rats
by Tammy M. Seasholtz, Tong Zhang, Michael R. Morissette, Amy L. Howes, Amy H.
Yang, and Joan Heller Brown
Circulation Research
Volume 89(6):488-495
September 14, 2001
Copyright © American Heart Association, Inc. All rights reserved.
Figure 1. Enhanced agonist-stimulated DNA synthesis in vessels and ASMCs from SHR versus
WKY. A, Serum- but not thrombin-stimulated [3H]thymidine incorporation was significantly
higher (*P<0.01) than control values in vessels from WKY rats.
Tammy M. Seasholtz et al. Circ Res. 2001;89:488-495
Copyright © American Heart Association, Inc. All rights reserved.
Figure 2. Selective increase in RhoA expression in vessels from SHR. The expression of RhoA
(A), Ras (B), Rho kinase (C), and Rho-GDIα (D) in aortic homogenates from adult SHR and WKY
(S and W, respectively) was measured by use of Western blot analysis.
Tammy M. Seasholtz et al. Circ Res. 2001;89:488-495
Copyright © American Heart Association, Inc. All rights reserved.
Figure 3. RhoA activity is elevated in aortas from SHR versus WKY rats.
Tammy M. Seasholtz et al. Circ Res. 2001;89:488-495
Copyright © American Heart Association, Inc. All rights reserved.
Figure 4. RhoA expression and Thr-stimulated RhoA activation are increased in ASMCs from
SHR. A, Western blot analysis of ASMCs from SHR and WKY revealed that total RhoA per mg
protein is higher in SHR. B, RhoA-RBD binding was used to measure activation of RhoA.
Tammy M. Seasholtz et al. Circ Res. 2001;89:488-495
Copyright © American Heart Association, Inc. All rights reserved.
Figure 5. RhoA expression and activity are increased in aortas from L-NAME–treated rats.
Tammy M. Seasholtz et al. Circ Res. 2001;89:488-495
Copyright © American Heart Association, Inc. All rights reserved.
Figure 6. Reduced expression of the CKI p27Kip1, but not p21Waf1/Cip1, in aortas from SHR.
Western blot analysis of aortic homogenates with use of an antibody to p27Kip1 (A) revealed a
doublet band at the expected molecular weight (inset: W indicates WKY; S, SHR).
Tammy M. Seasholtz et al. Circ Res. 2001;89:488-495
Copyright © American Heart Association, Inc. All rights reserved.
Figure 7. Levels of p27Kip1 are reduced by RhoA (L63RhoA) and PI3K (p110CAAX).
Tammy M. Seasholtz et al. Circ Res. 2001;89:488-495
Copyright © American Heart Association, Inc. All rights reserved.
Figure 8. Thr stimulates DNA synthesis and decreases levels of p27Kip1.
Tammy M. Seasholtz et al. Circ Res. 2001;89:488-495
Copyright © American Heart Association, Inc. All rights reserved.