Cardiovascular Research Advance Access [Accepted Manuscript] published online on December 11, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn340
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Differential effects of red and white wines on inhibition of the PDGF receptor: Impact of the mash fermentation
1 Klinik III für Innere Medizin, Universität zu Köln, Germany
2 Center for Molecular Medicine of the University of Cologne (CMMC), Germany
3 Institut für Pathologie, Universität zu Köln, Germany
4 Fachgebiet Weinanalytik und Getränkeforschung, Geisenheim, Germany
5 Medizinische Klinik III, Universitätskliniken des Saarlandes,Homburg/Saar, Germany
* corresponding author Address correspondence to: Stephan Rosenkranz, MD, Klinik III für Innere Medizin, Universität zu Köln, Kerpener Str. 62, 50924 Köln (Lindenthal), Germany, phone: +49-221-478-32402, FAX: +49-221-478-32400, e-mail: stephan.rosenkranz{at}uk-koeln.de
Aims: Moderate wine consumption is associated with a significant reduction of cardiovascular mortality. The molecular basis of this phenomenon remains unknown. Platelet-derived growth factor (PDGF) is an important contributor to atherogenesis. We investigated the effects of selected red and white wines on PDGF receptor (PDGFR) signaling in rat and human vascular smooth muscle cells (VSMCs).
Methods and Results: All red wines concentration-dependently inhibited the ligand-induced tyrosine phosphorylation of the PDGFR, downstream signaling events such as mitogen activated protein (MAP) kinase activation (Erk 1/2) and induction of immediate early genes (Egr-1, c-fos), and PDGF-induced cellular responses, whereas all white wines had no effect. At concentrations achieved after wine consumption in humans, all red wines completely abolished PDGF-dependent VSMC proliferation and migration. Red wines also inhibited PDGFR phosphorylation in vascular tissue, and in human coronary smooth muscle cells. Quantitative analyses of all tested wines and of samples collected at various time points (days 0-16) of the "mash fermentation", which is only performed for red wine, revealed that flavonoids of the catechin family, which potently inhibit PDGFR signaling, are extracted from grape seeds and skins during this process and therefore accumulate specifically in red wine. The accumulation of flavonoids correlated with the inhibitory potency of red wines on PDGFR signaling. Furthermore, this procedure could be imitated by incubation of wines with shredded grape seeds, and flavonoid-enriched white wine inhibited the PDGFR as potently as red wines.
Conclusions: Only red wines abrogate a critical pathogenic mechanism during atherogenesis, PDGFR signaling, in VSMCs. This effect is mediated by non-alcoholic constituents, which accumulate during the mash fermentation. Our findings offer a molecular explanation for the vasoprotective effects particularly of red wine. Therefore, future epidemiological studies should consider differential protective effects of red and white wine in vivo.
KEYWORDS atherosclerosis; platelet-derived growth factor (PDGF); tyrosine kinases; wine; French Paradox
Time for primary review: 25 Days
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  M. M. Dohadwala and J. A. Vita Grapes and Cardiovascular Disease J. Nutr., September 1, 2009; 139(9): 1788S - 1793S. [Abstract] [Full Text] [PDF]
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