title: 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.affiliation: Division of Cardiovascular Research, St. Elizabeth's Medical Center, Boston, Massachusetts, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Hixon
authors.forename: C
authors.initials: C
authors.lastname: Muro-Cacho
authors.forename: M W
authors.initials: MW
authors.lastname: Wagner
authors.forename: C
authors.initials: C
authors.lastname: Obejero-Paz
authors.forename: E
authors.initials: E
authors.lastname: Millie
authors.forename: Y
authors.initials: Y
authors.lastname: Fujio
authors.forename: Y
authors.initials: Y
authors.lastname: Kureishi
authors.forename: T
authors.initials: T
authors.lastname: Hassold
authors.forename: K
authors.initials: K
authors.lastname: Walsh
authors.forename: A
authors.initials: A
authors.lastname: Gualberto
mesh_terms: 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
chemical_list: 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