Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization
Mary L. Hixon, … , Kenneth Walsh, Antonio Gualberto
Mary L. Hixon, … , Kenneth Walsh, Antonio Gualberto
Published October 15, 2000
Citation Information: J Clin Invest. 2000;106(8):1011-1020. https://doi.org/10.1172/JCI8252.
View: Text | PDF
Article

Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization

Abstract

Vascular smooth muscle cells (VSMCs) at capacitance arteries of hypertensive individuals and animals undergo marked age- and blood pressure–dependent polyploidization and hypertrophy. We show here that VSMCs at capacitance arteries of rat models of hypertension display high levels of Akt1/PKB protein and activity. Gene transfer of Akt1 to VSMCs isolated from a normotensive rat strain was sufficient to abrogate the activity of the mitotic spindle cell–cycle checkpoint, promoting polyploidization and hypertrophy. Furthermore, the hypertrophic agent angiotensin II induced VSMC polyploidization in an Akt1-dependent manner. These results demonstrate that Akt1 regulates ploidy levels in VSMCs and contributes to vascular smooth muscle polyploidization and hypertrophy during hypertension.

Authors

Mary L. Hixon, Carlos Muro-Cacho, Mark W. Wagner, Carlos Obejero-Paz, Elise Millie, Yasushi Fujio, Yasuko Kureishi, Terry Hassold, Kenneth Walsh, Antonio Gualberto

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Akt1 overexpression in VSMCs by adenovirus gene transfer. (Top) Western ...
Akt1 overexpression in VSMCs by adenovirus gene transfer. (Top) Western blot analysis demonstrating overexpression of Akt1 constructs in adenovirus-infected aortic VSMCs isolated from 3-week-old WKY rats. Adenovirus containing β Gal, wild-type Akt1, and double-mutant T308A/S473A Akt1 (Akt1 AA) are described in Methods. Data are representative of two experiments. Other details as in Figure 1. (Bottom) Akt1 activity in control (β Gal) and Akt1-expressing VSMC. Experimental details as in Figure 1. Data are representative of two experiments.