Role of Endogenous Prostaglandins in Vascular Remodeling

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Mice lacking the prostaglandin (PG) I_2 receptor (IP ^<-/->) and wild-type control mice have been backcrossed to C57BL/6 mice more than 6 times, and all experiments were performed using 12-15-week-old (25-30 g) male mice. Mice were anesthetized with an intraperitoneal injection of ketamine HCl and xylazine. The left common carotid artery was ligated near the carotid bifurcation. All animals were killed 28 days after ligation of the carotid artery and fixed with 10 % formalin in PBS under constant pressure. Morphometric analyzes were performed on the carotid arteries, and the following parameters were measured: luminal area, area inside the inner elastic lamina (TEL) and area inside the external elastic lamina. The medial and intimal areas were calculated from these parameters.In non-ligated vessels, there was no difference of medial and intimal area between IP ^<-/-> mice and wild-type mice. The ratio of ligated and non-ligated intimal area was 112.9 in IP ^<-/-> mice and 3.6 in wild-type mice, respectively (P <0.0001). This ratio of medial area was 2.3 in IP ^<-/-> mice and 1.2 in wild-type mice, respectively (P<0.0001). In ligated vessels, the intimal/medial area ratio was 1.25 ± 0.34 (mean ± SE) in IP^<-/-> mice and 0.06 ± 0.03 in wild-type mice (P <0.0001). In IP ^<-/-> mice, the neointimal area as a percentage of the IEL cross section area was 58.5 ±12.4 % in IP ^<-/-> mice, which was significantly (P <0.0001) higher than that in wild-type mice (4.8 ± 2.4 %).The results show that significant suppression of ligation-induced neointimal formation by endogenous PGI_2. This means that endogenously produced PGI_2, plays an important role in ligation-induced vascular remodeling.