ORIGINAL ARTICLES  VASCULAR SECTION 

The Journal of Cardiovascular Surgery 2002 December;43(6):869-75

Copyright © 2009 EDIZIONI MINERVA MEDICA

language: English

Lipo-prostaglandin E1 is absorbed by vascular smooth muscle cells and may enhance re-endothelialization of vein grafts

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.