title: Cocoa procyanidins inhibit proliferation and angiogenic signals in human dermal microvascular endothelial cells following stimulation by low-level H2O2.
abstract: Procyanidins extracted from cocoa play a role in the defense against oxidative stress, as well as in vascular and immune functions. We previously reported that pentameric procyanidins isolated from cocoa inhibit the expression of the tyrosine kinase ErbB2 gene, thus slowing the growth of cultured human aortic endothelial cells. We herein investigate the further consequences of such inhibition by cocoa procyanidins, particularly regarding the protein level in phosphorylation patterns and the effects on the proliferation of human dermal microvascular endothelial cells (HDMECs) following angiogenic stimulation with low-level H2O2. We report herein that both the pentameric and octameric procyanidin fractions of cocoa inhibit the proliferation of HDMECs, whereas the pentameric fraction modulates the activity of several crucial proteins in angiogenic signaling by altering their tyrosine phosphorylation. Similar to aortic endothelial cells, the pentameric procyanidin fraction down-regulates the expression of ErbB2 tyrosine kinase in HDMECs. In conclusion, we report evidence suggesting that polyphenols may influence endothelial growth signaling, thus affecting angiogenesis in vitro. If these observations are applicable in vivo, they suggest a beneficial effect for cells overexpressing ErbB2, such as in specific neoplasias
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, California 95616, USA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Kenny
authors.forename: Carl L
authors.initials: CL
authors.lastname: Keen
authors.forename: Paul
authors.initials: P
authors.lastname: Jones
authors.forename: Hsing-Jien
authors.initials: HJ
authors.lastname: Kung
authors.forename: Harold H
authors.initials: HH
authors.lastname: Schmitz
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D044946:Biflavonoids; D002099:Cacao; D002392:Catechin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008833:Microcirculation / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D044945:Proanthocyanidins; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply*
chemical_list: D044946:Biflavonoids; D002392:Catechin; D017931:DNA Primers; D005419:Flavonoids; D006861:Hydrogen Peroxide; D044945:Proanthocyanidins; D018719:Erb-b2 Receptor Tyrosine Kinases; C404987:flavan-3-ol; C017674:procyanidin