Modulation of elastin expression by heparin is dependent on the growth condition of vascular smooth muscle cells: up-regulation of elastin expression by heparin in the proliferating cells is mediated by the inhibition of protein kinase C activity.
The effect of heparin on elastin expression in the proliferating and quiescent phases of growth of smooth muscle cells was studied. Heparin stimulated elastin synthesis and its mRNA level 2-3 fold in the proliferating cells while it inhibited the cell proliferation. The inhibition of cell proliferation and the stimulation of elastin expression by heparin in the proliferating cells were mimicked by a potent protein kinase C antagonist, H-7, but not by H-89, W-7, and HA1004, suggesting that the effect of heparin is mediated by the inhibition of protein kinase C. In contrast, heparin inhibited elastin synthesis and its mRNA level slightly but exhibited no effect on cell proliferation in the growth-arrested cells. This result indicates that heparin reciprocally affects elastin expression depending on the growth state of smooth muscle cells. Heparin thus exerts a complex influence on elastin expression in smooth muscle cells.
Wachi
H
H
Department of Clinical Chemistry, Hoshi College of Pharmacy, Tokyo.
Seyama
Y
Y
Tajima
S
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D004549:Elastin / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014333:Tropoelastin / Q000032:analysis; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D014333:Tropoelastin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D006493:Heparin; D004549:Elastin; D011493:Protein Kinase C