Vascular smooth muscle polyploidization--from mitotic checkpoints to hypertension.
Aging and hypertension are accompanied by an increase in mass and rigidity of arterial walls. At capacitance arteries, the enlargement and stiffness of the medial smooth muscle layer promote systolic hypertension and contribute to left ventricular hypertrophy and cardiovascular morbidity. Morphological studies have demonstrated that vascular smooth muscle cell (VSMC) hypertrophy, with minimal hyperplasia, causes the enlargement of vascular smooth muscle at capacitance arteries, and that VSMC hypertrophy is strongly associated with VSMC polyploidization. Recent studies demonstrate that hypertrophic signals, such as those elicited by Angiotensin II, abrogate the mechanisms of control of M phase in VSMC and induce cell cycle re-entry and polyploidization. These polyploid VSMC have a lower replicative rate, but a higher mass, protein content and matrix production than their diploid counterparts. Both, the protein kinase Aktl and the cyclin kinase-associated protein CKsl, have been implicated in the mechanism of VSMC polyploidization during hypertension. Here, we review the function of these proteins at the mitotic spindle cell cycle checkpoint and their role in the process of VSMC polyploidization.
Hixon
Mary L
ML
Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA.
Gualberto
Antonio
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018816:Genes, cdc; D006973:Hypertension / Q000235:genetics* / Q000473:pathology; D006984:Hypertrophy; D008938:Mitosis; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; C081185:CKS1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt