PSelectin Expression as a Molecular End Target of Ethanol Preconditioning

The Red Wine Diet

The Red Wine Diet

Get Instant Access

A likely effector target of the signaling cascade induced by antecedent ethanol ingestion is P-selectin expression. This adhesive glycoprotein is upregulated in postischemic tissues, where it participates in leukocyte recruitment by supporting leukocyte rolling, a requisite step for both subsequent establishment of stationary adhesive interactions and diapedesis across postcapillary venular endothelium. Ethanol preconditioning prevents P-selectin expression in postischemic tissues by an adenosine- and NO-triggered, oxidant-dependent mechanism. These observations provide the molecular basis for the antiadhesive actions demonstrated by ethanol preconditioning in the setting of I/R.

Bibliography

Albert, M. A., Glynn, R. J., and Ridker, P. M. (2003). Alcohol consumption and plasma concentration of C-reactive protein. Circulation 107, 443-447.

Das, D. K., and Ursini, F. (eds.). (2002). Alcohol and wine in health and disease. Ann. N. Y. Acad. Sci. 957, 1-350. A comprehensive selection of articles dealing with the cardioprotective actions associated with consumption of moderate levels of wine and other alcoholic beverages. Dayton, C., Yamaguchi, T., Warren, A., and Korthuis, R. J. (2002). Ischemic preconditioning prevents postischemic arteriolar, capillary, and postcapillary venular dysfunction: Signaling pathways mediating the adaptive metamorphosis to a protected phenotype in preconditioned endothelium. Microcirculation 9, 73-89. Dayton, C. B., Kamada, K., Yamaguchi, T., Carter, P., Gute, D. C., and Korthuis, R. J. (2004). Ethanol ingestion prevents postischemic P-selectin expression. Submitted for publication. Microcirculation 11, 209-718.

Granger, D. N. (1999). Ischemia-reperfusion: Mechanisms of microvascu-lar dysfunction and the influence of risk factors for cardiovascular disease. Microcirculation 6, 167-178. Korthuis, R. J. (ed.). (2004). Alcohol and cardioprotection. Pathophysiology (in press). A Special Topics supplement to the journal with concise reviews regarding the epidemiologic evidence for the cardioprotective effects of ethanol, mechanisms underlying its infarct-sparing and antiinflammatory actions of ethanol and the red wine constituent polyphe nol resveratrol, and the effects of ethanol on platelet function, fibrinolytic activity, and lipid metabolism. Pathophysiology 10, 81-145.

Shigematsu, S., Ishida, S., Hara, M., Takahashi, N., Yoshimatsu, H., Sakata, T., and Korthuis, R. J. (2003). Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants. Free Radic. Biol. Med. 34, 810-817.

Wallerath, T., Poleo, D., Li, H., and Forstermann, U. (2003). Red wine increases the expression of human endothelial nitric oxide synthase: A mechanism that may contribute to its beneficial cardiovascular effects. J. Am. Coll. Cardiol. 41, 471-478.

Yamaguchi, T., Dayton, C., Shigematsu, T., Carter, P., Yoshikawa, T., Gute, D. C., and Korthuis, R. J. (2002). Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell adhesive interactions. Am. J. Physiol. 283, H1019-H1030. The first description of the effect of ethanol to promote the development of an anti-inflammatory phenotype in the microcirculation and the critical role that adenosine A2 receptor—dependent activation of endothelial nitric oxide synthase plays in this adaptive transformation.

Yamaguchi, T., Dayton, C. B., Ross, C. R., Yoshikawa, T., Gute, D. C., and Korthuis, R. J. (2003). Late preconditioning by ethanol is initiated by an oxidant-dependent signaling pathway. Free Radic. Biol. Med. 34, 365-376.

Capsule Biography

Dr. Korthuis is the Bolm Distinguished Professor and Chairman of the Department of Medical Pharmacology and Physiology at the University of Missouri-Columbia. His research is directed at elucidating the cellular mechanisms that underlie the development of protected phenotypes in the microcirculations of the small intestine and skeletal muscle in response to ischemic preconditioning and antecedent ethanol ingestion. Dr. Korthuis' work is supported by grants from the National Institutes of Health (HL-54797 and DK-43785).

Was this article helpful?

0 0
Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook


Post a comment