title: Mitogenesis of vascular smooth muscle cell stimulated by platelet-derived growth factor-bb is inhibited by blocking of intracellular signaling by epigallocatechin-3-O-gallate.
abstract: Epigallocatechin gallate (EGCG) is known to exhibit antioxidant, antiproliferative, and antithrombogenic effects and reduce the risk of cardiovascular diseases. Key events in the development of cardiovascular disease are hypertrophy and hyperplasia according to vascular smooth muscle cell proliferation. In this study, we investigated whether EGCG can interfere with PDGF-bb stimulated proliferation, cell cycle distribution, and the gelatinolytic activity of MMP and signal transduction pathways on RAOSMC when it was treated in two different ways-cotreatment with PDGF-bb and pretreatment of EGCG before addition of PDGF-bb. Both cotreated and pretreated EGCG significantly inhibited PDGF-bb induced proliferation, cell cycle progression of the G0/G1 phase, and the gelatinolytic activity of MMP-2/9 on RAOSMC. Also, EGCG blocked PDGF receptor-β (PDGFR-β) phosphorylation on PDGF-bb stimulated RAOSMC under pretreatment with cells as well as cotreatment with PDGF-bb. The downstream signal transduction pathways of PDGFR-β, including p42/44 MAPK, p38 MAPK, and Akt phosphorylation, were also inhibited by EGCG in a pattern similar to PDGFR-β phosphorylation. These findings suggest that EGCG can inhibit PDGF-bb stimulated mitogenesis by indirectly and directly interrupting PDGF-bb signals and blocking the signaling pathway via PDGFR-β phosphorylation. Furthermore, EGCG may be used for treatment and prevention of cardiovascular disease through blocking of PDGF-bb signaling.
authors.affiliation: Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Byeong-Ju
authors.initials: BJ
authors.lastname: Kwon
authors.forename: Min-Ah
authors.initials: MA
authors.lastname: Koo
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: You
authors.forename: Jong-Chul
authors.initials: JC
authors.lastname: Park
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D000077214:Becaplermin; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008934:Mitogens / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D020011:Protective Agents / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008934:Mitogens; D020011:Protective Agents; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D002392:Catechin; C045651:epigallocatechin gallate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9