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 1

Options: View larger image (or click on image) Download as PowerPoint
Akt1 protein levels and activity are upregulated in vascular smooth musc...
Akt1 protein levels and activity are upregulated in vascular smooth muscle of hypertensive rats. (a–d) Western blot analysis of Akt1 protein in aortic VSMCs freshly isolated from 3-week-old WKY and SHR rats (a), 4-month-old WKY and SHR rats (b), 4-month-old WKY and WKY-Goldblatt rats (c), and 4-month-old Zucker lean and fa/fa rats (d). As a control, blots were probed for β-actin expression. Each lane represents Akt1/β-actin levels in protein extracts of VSMCs isolated from the upper two-thirds of the thoracic aorta of nine animals; n.s., nonspecific, band reactive with secondary Ab. Western blotting was carried out as indicated in Methods. Three hundred fifty micrograms of protein extract was employed in gel in c and 200 μg in gels used in a, b, and d. Goldblatt-WKY rats underwent left renal artery constriction for 6 weeks (mean blood pressure [MBP] = 123 ± 4, sham-operated; MBP = 180 ± 12, Goldblatt). MBPs of WKY, SHR, and Zucker animals were within the range shown in Table 1. Parts a and b are representative of three preparations and c is representative of two preparations. (d) Two independent preparations of Zucker lean and fa/fa rats. (e) Akt1 activity in 4-month-old control (WKY and Zucker lean) and hypertensive rats (SHR and Zucker fa/fa). Activity was measured as histone H2B phosphorylation, as indicated in Methods. Bars indicate PhosphorImager scans of phosphorylated histone H2B bands in arbitrary units relative to Akt1 activity in extracts of Zucker lean animals. Data are representative of three independent experiments.