Growth inhibition of human tumor cell lines by antisense oligonucleotides designed to inhibit p120 expression

Using a rat model of short- (4 weeks) and long-term (10 weeks) ascending aortic banding and debanding, we examined the relationship between coronary dilator reserve and morphological vascular changes. After 4 or 10-week banding, in vivo systolic left ventricular pressure and ventricular wt/body wt ratio increased to a similar level, compared with controls. The coronary dilator reserve measured in an isolated heart preparation decreased similarly in the two banded groups, compared with controls. The ratios of medial to luminal area and perivascular collagen to luminal area in coronary microvessels increased in the banded groups. At 4 weeks after debanding, cardiac hypertrophy regressed to the control level, and the duration of banding did not alter the extent of the regression. The coronary dilator reserve normalized in the group debanded after 4-week banding, but did not regress in the group debanded after 10-week banding. In both of the debanded groups, the hypertrophied media regressed completely. The increased perivascular collagen regressed almost completely in the group debanded after 4-week banding, but remained greater in the group debanded after 10-week banding than in the controls. From these results, we conclude that (i) the regression of medial hypertrophy does not always improve the decreased coronary dilator reserve, and (ii) the vascular fibrosis may be the major cause of the irreversibility of decreased coronary dilator reserve in long-term cardiac hypertrophy.