Suppression of oxidized LDL-induced PDGF receptor beta activation by ginkgo biloba extract reduces MMP-1 production in coronary smooth muscle cells.
ABSTRACT 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.
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.
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.
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.
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ABSTRACT: E Fragopoulou1, C A Demopoulos2, S Antonopoulou11Department of Science of Nutrition-Dietetics, Harokopio University, Athens, Greece; 2Faculty of Chemistry, National and Kapodistrian University of Athens, Athens, GreeceAbstract: The “French paradox” is the observation that the French suffer a relatively low incidence of coronary heart disease, despite having a diet relatively rich in saturated fats. Several theories have been proposed in order to explain this phenomenon and several debates arose. One of them attributed this phenomenon to the regular and moderate consumption of wine in France. More specific, it is thought that the existence of bioactive compounds in wine could have an effect on the cardiovascular system, preventing or delaying atherosclerosis. The mechanisms mediating these beneficial effects include: low-density lipoprotein oxidation; endothelium function; smooth muscle cells proliferation; platelet aggregation and angiogenesis. Several mediators participate in these pathophysiological mechanisms, among them are plateletactivating factor (PAF) and oxidized phospholipids that play a crucial and essential role in the initiation and the progression of atherogenesis. In this review, apart from the already known and well characterized biological effects of wine bioactive compounds, the co-existence of compounds that could modulate the production and the actions of PAF is highlighted. The existence of bioactive compounds in wine that could reduce PAF production and inhibit its actions may offer a new insight into the well known French paradox and expand the already reported mechanisms by including the inhibition of PAF actions.Keywords: wine, bioactive compounds, lipids, platelet-activating factor, atherosclerosisInternational Journal of Wine Research. 01/2009;