Lipo-prostaglandin E1 is absorbed by vascular smooth muscle cells and may enhance re-endothelialization of vein grafts.
BACKGROUND
Enhancement of re-endothelialization inhibits the progression of intimal hyperplasia. We investigated uptake of Lipoprostaglandin E(1) (LPGE(1)) by endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and effects of the LPGE(1) 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-LPGE(1) (DLPGE(1)); 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 microg/kg LPGE(1) 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 DLPGE(1), whereas the ECs revealed no fluorescence. In flow cytometry, histograms of VSMCs showed a specific notch of DLPGE(1), 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 LPGE(1) is predominantly absorbed by the VSMCs and exuded PGE(1) then acts on the VSMCs itself and on ECs alike. The %EC at 7 days was 58.4+/-1.9% in the DLPGE(1) group and 31.6+/-6.8% in controls (p<0.05) showing a significant enhancing effect of DLPGE(1) on re-endothelialization of the vein grafts.


CONCLUSIONS
In an animal model, daily administration of LPGE(1) resulted in significant enhancement of vein graft re-endothelialization. LPGE(1) was absorbed by the VSMCs, whereas the ECs showed no uptake, therefore the enhancement is probably due to a paracrine effect of VSMCs.
Akasaka
N
N
Department of Surgery, Asahikawa Medical University, Asahikawa, Japan.
Yamazaki
K
K
Ishikawa
M
M
Koya
A
A
Hirasawa
M
M
Inaba
M
M
Goh
K
K
Sasajima
T
T
D000527:Alprostadil / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D001026:Coronary Artery Bypass / Q000009:adverse effects / Q000379:methods*; D003327:Coronary Disease / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006083:Graft Occlusion, Vascular / Q000473:pathology* / Q000517:prevention & control; D007601:Jugular Veins / Q000473:pathology* / Q000637:transplantation*; D008297:Male; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011336:Probability; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D000527:Alprostadil