From Venus and Mars: Gender Specific Analysis of Blood Platelets

Cardiovascular disease epidemiological studies reveal compelling evidence that this disease is strongly influenced by gender. Other laboratory based studies have suggested that gender disparities can also be detected in platelet physiological measurements. These observations have led us to ask whether gender differences may play a role in platelet quality and integrity during storage. We have applied proteomic approaches to gain an understanding of the molecular mechanisms of gender-specific platelet signal transduction and its potential significance to transfusion medicine. Buffy coat platelet concentrates (N=4) pooled from four male or female donors, respectively, were analyzed by 2D gel electrophoresis and revealed 15 reproducible protein differences between their individual platelet proteomes. Validation by western blot analysis confirmed the proteomic data demonstrating differences in the expression profiling of proteins including 14-3-3, myosin, platelet factor 4 and SH3-domain binding protein glutamic acid-rich like protein as well as in posttranslational modification of proteins including pleckstrin and 14-3-3. These findings spurred a more detailed gender-specific analysis of single donors. In vitro measures (N=28 of each gender) for platelet function revealed that female platelets showed an averaged 15% higher level of activation as well as GPIIb/IIIa activation monitored by CD62P or Pac-1 binding, respectively. This point towards differences in signal transduction and western blot analyses of the platelet proteome of these individuals showed an averaged two to three-fold higher expression of signaling proteins including 14-3-3, Rap1, RhoA and RhoGDI. Furthermore, female platelets contain a two-fold higher level of activated Rap1 supporting the gender-influenced signaling hypothesis. To test whether these gender-specific results might have an impact on transfusion medicine, biochemical analyses of buffy coat platelet concentrates during storage were carried out. Preliminary data indicate that female platelets maintain the higher level of platelet activation during a 7-day storage period paralleled with elevated metabolic activity as monitored by glucose and lactate levels, respectively. These data can be used to assess other potential molecular mechanisms underlying the differences in the gender-specific signaling platelet proteome. Thus far, the clinical significance of these findings in transfusion medicine is unknown.