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Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
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Akasaka N., Yamazaki K., Ishikawa M., Koya A., Hirasawa M., Inaba M., Goh K., Sasajima T.
Department of Surgery, Asahikawa Medical University, Asahikawa, Japan
Background. Enhancement of re-endothelialization inhibits the progression of intimal hyperplasia. We investigated uptake of Lipoprostaglandin E1 (LPGE1) by endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and effects of the LPGE1 on re-endothelialization of vein grafts.
Methods. Primary cultured ECs and VSMCs were obtained from mongrel dogs, and incubated in mediums containing 0.5, 5, 50, and 250 ng/ml of DiI-LPGE1 (DLPGE1); its uptake was visualized by the standard rhodamine excitation, and assessed by flow cytometry. In an implantation study, the bilateral femoral veins of 18 animals were implanted into the femoral artery, and the animals were given 0.2 μg/kg LPGE1 for 2 weeks. Percentages of EC coverage area of the grafts (%EC) were measured by silver nitrate staining at intervals of 3, 7, and 21 days after implantation.
Results. VSMCs showed significant uptake in all of the mediums containing DLPGE1, whereas the ECs revealed no fluorescence. In flow cytometry, histograms of VSMCs showed a specific notch of DLPGE1, which increased the height according to the grade of the concentrations. The notch did not appear in the histograms of the ECs incubated with any concentration nor in the VSMCs incubated in control medium. These results suggested that LPGE1 is predominantly absorbed by the VSMCs and exuded PGE1 then acts on the VSMCs itself and on ECs alike. The %EC at 7 days was 58.4±1.9% in the DLPGE1 group and 31.6±6.8% in controls (p<0.05) showing a significant enhancing effect of DLPGE1 on re-endothelialization of the vein grafts.
Conclusions. In an animal model, daily administration of LPGE1 resulted in significant enhancement of vein graft re-endothelialization. LPGE1 was absorbed by the VSMCs, whereas the ECs showed no uptake, therefore the enhancement is probably due to a paracrine effect of VSMCs.