Growth response of tetraploid smooth muscle cells to balloon embolectomy-induced vascular injury in the spontaneously hypertensive rat.

Previous studies in this laboratory have demonstrated that smooth muscle hypertrophy in large arteries of hypertensive animals is accompanied by development of polyploidy in a large fraction of the smooth muscle cell population. The present studies address whether there is an inherent loss in the ability of tetraploid cells to respond to proliferative stimuli by examining whether these cells initiate DNA replication after balloon catheter-induced vascular injury. Left carotid arteries of 5- to 7-month-old spontaneously hypertensive rats were subjected to balloon injury, and the animals were perfused intravenously with [3H]thymidine for 32 h. The animals were killed, and smooth muscle cells were isolated from carotid medial preparation by enzymatic digestion. Cells were processed for simultaneous autoradiographic analysis of [3H]thymidine incorporation and fluorometric analysis of cellular DNA content as a means of simultaneously assessing both the ploidy level of a cell and whether or not it had initiated DNA replication in response to balloon injury. Results demonstrated the presence of [3H]thymidine-labeled cells with DNA contents that were greater than 4C but less than 8C (p less than 0.01), indicating that they are cycling tetraploid cells. These data demonstrate that tetraploid smooth muscle cells in vivo are capable of initiating DNA synthesis in response to balloon injury. Results indicate that there is not an inherent loss in the capacity of tetraploid cells to respond to a proliferative stimulus, although it remains to be determined whether the polyploid cells that initiate DNA replication after balloon injury actually go on to divide.