Plasmin stimulates expression of endothelin-1 mRNA and endothelin-1 release in vascular endothelial cells.
Incubation of cultured porcine aortic endothelial cells (ECs) with plasmin resulted in a significant and concentration-dependent increase in endothelin-1 (ET-1) release from the cells. This increasing effect was completely inhibited by aprotinin but not by tranexamic acid, thereby suggesting that the plasmin-induced stimulation of ET-1 release requires the catalytic site but not the lysine binding site, in plasmin molecule. Plasmin stimulated the expression of prepro ET-1 mRNA in ECs. Actinomycin D chase experiments suggested that enhanced stability of ET-T mRNA could not account for the above plasmin-induced stimulation. It is likely that plasmin potentiates the endothelial ET-1 production, probably by the stimulation of ET-1 gene transcription. It remains to be seen whether the endothelial ET-1 production is enhanced after the thrombolytic therapy.
Matsumura
Y
Y
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Takada
K
K
Murakami
A
A
Takaoka
M
M
Morimoto
S
S
D000818:Animals; D001011:Aorta; D007611:Aprotinin / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007700:Kinetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011863:Radioimmunoassay; D013552:Swine; D014148:Tranexamic Acid / Q000494:pharmacology
D016232:Endothelins; D012333:RNA, Messenger; D014148:Tranexamic Acid; D007611:Aprotinin; D005341:Fibrinolysin