Suppression of oxidized LDL-induced PDGF receptor beta activation by ginkgo biloba extract reduces MMP-1 production in coronary smooth muscle cells.
OBJECTIVE
An extract of Ginkgo Biloba L. was shown to have preventive effects on cardiovascular disorders, but the molecular mechanisms of its actions remain to be elucidated. Since matrix metalloproteinases (MMPs) are implicated in the rupture of atherosclerotic plaques and the subsequent occurrence of acute coronary syndrome, we examined the effects of a leaf extract (Ginkgolon-24) on the production of MMP-1 in human coronary smooth muscle cells stimulated with oxidized low-density lipoprotein (oxLDL) and 4-hydroxynonenal, which are factors proposed to play a pivotal role in atherogenesis.


METHODS
The production of MMP-1 and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 were estimated by immunoblotting. The tyrosine-phosphorylated form of platelet-derived growth factor receptor beta (PDGFR-beta) was analyzed by immunoprecipitation of the receptor followed by immunoblotting.


RESULTS
oxLDL and 4-hydroxynonenal accelerated the production of MMP-1 with the preceding phosphorylation of ERK1/2 and PDGFR-beta;. Pretreatment with Ginkgolon-24 inhibited the production of MMP-1 and phosphorylation of ERK1/2 induced by oxLDL and 4-hydroxynonenal, but did not affect the production and phosphorylation induced by phorbol ester. Furthermore, Ginkgolon-24 prevented tyrosine phosphorylation of the receptor induced by oxLDL and 4-hydroxynonenal.


CONCLUSIONS
These results suggest that Ginkgo Biloba extract suppresses the oxLDL- and 4-hydroxynonenal-induced production of MMP-1, probably through the inhibition of PDGFR-beta activation in human coronary smooth muscle cells.
Akiba
Satoshi
S
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Kyoto, Japan. akiba@mb.kyoto-phu.ac.jp
Yamaguchi
Hidenori
H
Kumazawa
Satomi
S
Oka
Mayuko
M
Sato
Takashi
T
D000447:Aldehydes / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D020441:Ginkgo biloba / Q000737:chemistry*; D006801:Humans; D047468:Immunoprecipitation; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology; D010936:Plant Extracts / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism*
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D008077:Lipoproteins, LDL; D010936:Plant Extracts; C099252:oxidized low density lipoprotein; D017479:Receptors, Platelet-Derived Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D020781:Matrix Metalloproteinase 1; C027576:4-hydroxy-2-nonenal