Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization.
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.
Hixon
M L
ML
Division of Cardiovascular Research, St. Elizabeth's Medical Center, Boston, Massachusetts, USA.
Muro-Cacho
C
C
Wagner
M W
MW
Obejero-Paz
C
C
Millie
E
E
Fujio
Y
Y
Kureishi
Y
Y
Hassold
T
T
Walsh
K
K
Gualberto
A
A
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000473:pathology; D006973:Hypertension / Q000235:genetics* / Q000473:pathology; D006984:Hypertrophy; D008638:Mesenteric Arteries / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000473:pathology*; D009153:Mutagens / Q000494:pharmacology; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011924:Rats, Zucker; D011994:Recombinant Proteins / Q000096:biosynthesis; D015854:Up-Regulation
D009153:Mutagens; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D000804:Angiotensin II; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt