Tetraploid cells reach large sizes, probably because they extend their cell cycles at the G1 phase, a period when cells accumulate mass. Higher ploidy cells are observed at some developmental stages or cell lineages in many organisms, including humans, but tetraploid cells are rare in most normal human tissues. Hypertension greatly increases the prevalence of these large, tetraploid cells in these vessels in humans, and Hixon and colleagues now show that the same is true of several animal models of hypertension.
Following up on evidence that angiotensin is required for the effects of hypertension on the SMC cell cycle, these authors also demonstrate that expression of the protein kinase Akt1, a known mediator of angiotensin function, is elevated in capacitance arteries of hypertensive animals. Because the mitotic spindle checkpoint normally protects cells from undergoing extra rounds of DNA synthesis, Hixon et al. expressed Akt1 in primary SMCs and tested the ability of these cells to activate the mitotic spindle checkpoint in response to microtubule-depolymerizing agents.
They report that cyclin B, a cell cycle regulator that participates in this checkpoint, is degraded prematurely in Akt1-expressing cells, despite the presence of these drugs. Furthermore, these cultures accumulate large, tetraploid cells even when they are not treated with spindle-damaging drugs, suggesting that increased Akt1 function is sufficient to produce this cellular phenotype in hypertensive or even in aging normotensive arteries.
Journal
Journal of Clinical Investigation