Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy andpolyploidization

Vascular smooth muscle cells (VSMCs) at capacitance arteries of hypertensiv e individuals and animals undergo marked age- and blood pressure-dependent polyploidization and hypertrophy. We show here that VSMCs at capacitance ar teries of rat models of hypertension display high levels of Akt1/PKB protei n 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. Furtherm ore, the hypertrophic agent angiotensin II induced VSMC polyploidization in an Akt1-dependent manner. These results demonstrate that Akt1 regulates pl oidy levels in VSMCs and contributes to vascular smooth muscle polyploidiza tion and hypertrophy during hypertension.