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.
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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

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Figure 5

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Unscheduled cyclin B degradation in Akt1 wt–transduced VSMCs. VSMCs infe...
Unscheduled cyclin B degradation in Akt1 wt–transduced VSMCs. VSMCs infected with adenoviruses β Gal (a), T308A/S473A Akt1 mutant (b), AA Akt1 mutant, or wild-type Akt1 (c) were synchronized as above, then incubated at low density (1–2 × 104 cells/cm2) in 10% FBS in the absence or presence of 100 ng/ml colcemid and harvested at the indicated intervals. Colcemid was added at 16 hours after cell passage. Western blotting of cyclin B was carried out as indicated in Methods. Data are representative of three independent experiments.