Increase of Migration of Cultured Endothelial Cells by Angiotensin-Converting Enzyme Inhibitor Derived from Tuna Muscle

Abstract

The influence of angiotensin-converting enzyme (ACE) inhibitory octapeptide derived from tuna muscle (tuna AI) on the bovine aorta endothelial cell (BAEC) migration was investigated, as compared with captopril. BAEC migration was quantitated 6 d after release from contact inhibition by a teflon fence assay. The cultur e grown in the presence of tuna AI (1 and 10 iim) clearly exhibited an increase in migration, compared with the control. The media collected from tuna AI (1 and 10/iM)-stimulated BAECs significantly exhibited the interleukin (IL) - 1 activity that was detected by the thymocyte costimulation assay with phytohemagglutinin. Alth ough tuna AI was a weaker ACE inhibitor than captopril, the increasing effect of tuna AI on the migration and the IL-1 generation in BAECs was slightly greater than that of captopril. In quiescent BAECs, tuna AI (1 iim) apparently induced c-myc and platelet derived growth factor (PDGF) A-chain messenger ribonucleic acid (mRNA) expressions within 30 min, which persisted for 6 h. In contrast, captopril induced a very low expression of c-myc mRNA, and had no relation to PDGF A-chain mRNA ex pression. These results suggest that the increase of BAEC migration by tuna AI, unlike captopril, is likely related to the induction or activation of IL-1, and c-myc and PDGF mRNAs, in addition to the inhi- bition of the conversion of endogenous angiotensin I to angiotensin II. © 1992, The Pharmaceutical Society of Japan. All rights reserved.