Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension

Although abnormal cell growth in arterial vessel walls underpins vascular r emodeling in high blood pressure, the molecular basis of the abnormality in hypertension has not been fully defined. Here, we report that in the aorta of spontaneously hypertensive rats, telomerase is selectively activated an d telomeres are lengthened, in vivo and in vitro. Down-regulation of telome rase, the ribonucleoprotein complex responsible for the maintenance and elo ngation of telomeres (the ends of chromosomes) arrests the increased prolif eration of spontaneously hypertensive rat vascular smooth muscle cells and induces apoptosis. This apoptosis is reversible by overexpressing telomeras e and is prevented by increasing p53 tumor suppressor protein expression an d worsened by lowering p53. Telomerase activation, telomere maintenance, an d the p53 checkpoint appear to be critical for increased vascular smooth mu scle proliferation, thus they represent potential novel therapeutic targets in hypertension.