Gender Dependence for a Subset of the Low-Abundance Signaling Proteome in Human Platelets

Eidelman, Ofer; Jozwik, Catherine; Huang, Wei; Srivastava, Meera; Rothwell, Stephen W.; Jacobowitz, David M.; Ji, Xiaoduo; Zhang, Xiuying; Guggino, William; Wright, Jerry; Kiefer, Jeffrey; Olsen, Cara; Adimi, Nima; Mueller, Gregory P.; Pollard, Harvey B.

doi:10.4061/2010/164906

Gender Dependence for a Subset of the Low-Abundance Signaling Proteome in Human Platelets

Ofer Eidelman oeidelman{at}usuhs.mil¹
Catherine Jozwik cjozwik{at}usuhs.mil¹
Wei Huang whuang{at}usuhs.mil¹
Meera Srivastava msrivastava{at}usuhs.mil¹
Stephen W. Rothwell srothwell{at}usuhs.mil¹
David M. Jacobowitz djacobowitz{at}usuhs.mil²
Xiaoduo Ji xji{at}usuhs.mil¹
Xiuying Zhang xzhang{at}usuhs.mil¹
William Guggino wguggino{at}jhmi.edu³
Jerry Wright jwright{at}jhmi.edu³
Jeffrey Kiefer jkiefer{at}tgen.org⁴
Cara Olsen colsen{at}usuhs.mil⁵
Nima Adimi nadimi{at}usuhs.mil¹
Gregory P. Mueller gmueller{at}usuhs.mil¹
Harvey B. Pollard hpollard{at}usuhs.mil¹

¹Department of Anatomy, Physiology and Genetics, USU Center for Medical Proteomics, Uniformed Services University, School of Medicine, USUHS, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
²National Institute for Mental Health, NIH, 9500 Rockville Pike, Bethesda, MD 20892, USA
³Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
⁴Translational Genomics Research Institute, Phoenix, AZ 85004, USA
⁵Department of Preventive Medicine and Biometrics, Uniformed Services University School of Medicine, USUHS, 4301 Jones Bridge Road, Bethesda, MD 20814, USA

Abstract

The incidence of cardiovascular diseases is ten-times higher in males than females, although the biological basis for this gender disparity is not known. However, based on the fact that antiplatelet drugs are the mainstay for prevention and therapy, we hypothesized that the signaling proteomes in platelets from normal male donors might be more activated than platelets from normal female donors. We report here that platelets from male donors express significantly higher levels of signaling cascade proteins than platelets from female donors. In silico connectivity analysis shows that the 24 major hubs in platelets from male donors focus on pathways associated with megakaryocytic expansion and platelet activation. By contrast, the 11 major hubs in platelets from female donors were found to be either negative or neutral for platelet-relevant processes. The difference may suggest a biological mechanism for gender discrimination in cardiovascular disease.