Inhibition of the PDGF beta-receptor tyrosine phosphorylation and its downstream intracellular signal transduction pathway in rat and human vascular smooth muscle cells by different catechins.
Abnormal proliferation of vascular smooth muscle cells (VSMC) as well as the platelet-derived growth factor (PDGF) plays an important role in the development of proliferative cardiovascular diseases. In this study, we show that treatment of rat and human aortic VSMC with 50 microM 2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol (catechin) and epicatechin (EC) fails to inhibit the PDGF-Rb-activated intracellular signal transduction pathway and VSMC growth. In contrast, 10-50 microM epigallocatechin-3 gallate (EGCG), epicatechin-3 gallate (ECG), and catechin-3 gallate (CG), which all have a galloyl group in the 3-position of the catechin structure, effectively inhibit tyrosine-phosphorylation of PDGF-Rb, PI 3'-K, and PLC-gamma1 as well as the PDGF-BB-induced increase in [Ca2+]i. The PDGF-BB-induced increase in DNA synthesis and cell number was inhibited by ECG, EGCG, and CG, but not by catechin and EC. Epigallocatechin (EGC) that has a galloyl group in the 2-position effectively inhibited VSMC growth without affecting the PDGF-Rb signal pathway. A reduction of 45% and 70% of the intimal and medial cell number in the S-phase, respectively, has been observed in the catheter-injured left carotid artery 7 days after treatment of Wistar Kyoto rats with 10 mg/day EGCG. These results suggest that the galloyl group in the P3-position of the catechin structure is essential for inhibiting the PDGF-Rbeta-mediated intracellular signal transduction pathway.
Sachinidis
Agapios
A
Center of Physiology and Pathophysiology, University of Cologne, 50931 Cologne, Germany. A.Sachinidis@uni-koeln.de
Skach
Romanita Adriana
RA
Seul
Claudia
C
Ko
Yon
Y
Hescheler
Jürgen
J
Ahn
Hee-Yul
HY
Fingerle
Jürgen
J
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000077214:Becaplermin; D001973:Bromodeoxyuridine / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002452:Cell Count; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011921:Rats, Inbred WKY; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D014443:Tyrosine; C417939:catechin gallate; D002392:Catechin; D004247:DNA; C062669:epicatechin gallate; C045651:epigallocatechin gallate; D020797:Receptor, Platelet-Derived Growth Factor beta; D001973:Bromodeoxyuridine; D002118:Calcium