Vascular cell kinetics in response to intimal injury ex vivo.

Background: Recent studies indicate that the smooth muscle-like cells contributing to neointimal hyperplasia after vascular injury derive from circulating precursor cells. Here, we define the time course of precursor cell influx, the roles of separate vascular layers, and the relative role of migration versus proliferation to intimal hyperplasia.

Methods And Results: After rat aortic denudation injury the neointimal cell number increased several 100-fold between days 4 and 28, preceded by a 5-fold increase in the number of adventitial cells and a 4-fold increase in the number of adventitial microvessels.

Mechanisms behind the synergistic effect of sirolimus and imatinib in preventing restenosis after intimal injury.

Background: We have shown that the combination of sirolimus and imatinib synergistically inhibits denudation-induced neointimal hyperplasia in rats. We have now dissected the mechanisms behind this synergy and evaluated its long-term efficacy.

Methods: After aortic denudation injury, rats received established submaximal doses of sirolimus (1.

Vasculoprotective effects of somatostatin receptor subtypes.

We have shown that somatostatin agonist peptide CH275, selective to somatostatin receptor (sst) subtypes 1,4, was more effective in preventing intimal hyperplasia than the sst2,3,5-selective octreotide, raising the question what are the separate roles of the sst1- and 4-subtypes. Here, we dissect this observation further with highly subtype-selective peptidomimetics and demonstrate that, after rat carotid denudation, both the sst1- and 4-selective analogs (300 microg/kg/day, s.c.