[Effects of de-endothelialization and angiotensin II on the vascular remodeling in a model of rabbit aorta organ culture].
The effects of de-endothelialization and angiotensin II (A II) on smooth muscle cell (SMC) growth are still controversial. Cell culture experiments suggest an hypertrophic effect of AII, whereas in vivo experiments in de-endothelialized arteries using angiotensin converting enzyme inhibitors suggest a possible role of AII on proliferation and/or migration of SMC. Phenotype of SMC in culture does not necessarily reflect that in the whole organ. Yet, in vivo models are too complex to permit conclusions as to the proper effect of AII or endothelium. Therefore, we examined the effect of de-endothelialization and AII on SMC growth in an organ culture of vessel wall. Rabbit thoracic descending aortas (n = 42) held at their in vivo length, perfused at 40 ml/min and pressurized to 70 mmHg (P70) were maintained in DME medium supplemented with 20% fetal calf serum for periods of time varying between 0 and 15 days. In another group (n = 26), aortas were relaxed and not pressurized (P0). In each group, some arteries were de-endothelialized; 21 arteries were exposed to AII (10(-6) M) and indomethacin (10(-5) M) during the incubation. SMC proliferation was evaluated by 3H-thymidine uptake by the vessel wall. Statistics were performed using covariance analysis. In P0 group, de-endothelialization or AII had no effect on the vessel wall. In P70 group, de-endothelialization or led to a significant increase in media area which was reported to extracellular matrix synthesis and in 3H-thymidine uptake (p < 0.005) which peaked at 3-5 days and returned to basis levels at 6-8 days. All had no effect on 3H-thymidine uptake (p = 0.516) in P70 group. Our results obtained in rabbit aortic organ culture suggest that de-endothelialization induces SMC growth depending on pressure and/or wall stretching. AII, per se, had no additional effect on SMC growth in this model.
Karrillon
G J
GJ
INSERM U 141, hôpital Lariboisière, Paris.
Merval
R
R
Duriez
M
M
Tedgui
A
A
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D004247:DNA / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009924:Organ Culture Techniques; D011817:Rabbits; D013936:Thymidine / Q000493:pharmacokinetics
D000804:Angiotensin II; D004247:DNA; D013936:Thymidine
Effets de la désendothélialisation et de l'angiotensine II sur le remodelage vasculaire dans un modèle d'aorte de lapin en culture organotypique.