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ORIGINAL RESEARCH ARTICLE

Cocoa Procyanidins Inhibit Proliferation and Angiogenic Signals in Human Dermal Microvascular Endothelial Cells Following Stimulation by Low-Level H₂O₂

Thomas P. Kenny^*, Carl L. Keen, Paul Jones, Hsing-Jien Kung, Harold H. Schmitz and M. Eric Gershwin^*,1

^* Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, and Department of Nutrition, University of California at Davis, Davis, California 95616; Mars, Inc., McLean, Virginia 22101; and University of California at Davis Cancer Center, Sacramento, California 95817

To whom requests for reprints should be addressed at ¹ Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, TB 192, Davis, CA 95616. E-mail: megershwin{at}ucdavis.edu

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

Key Words: cocoa • angiogenesis • procyanidins