Distinct plasma proteomic changes in male and female African American stroke patients

Stroke occurs more often and results in more severe brain injury in African Americans than in Caucasians. The former also exhibit different responses to thrombolytic therapy than the latter do. There is an imminent need for stroke biomarkers for African Americans, who have been underrepresented in biomarker research for stroke diagnosis and prognosis. Proteomics offers sources for protein biomarkers that are not available by other Omics approaches. In this pilot study, plasma proteomes of African American stroke patients were analyzed and compared to that of hypertensive, non-stroke controls.

Plasma samples were prepared from whole blood specimens that were collected from stroke patients admitted to Grady Memorial Hospital in Atlanta, and their age- and sex-matched, hypertensive controls from the outpatient clinic. Samples were pooled according to patient groups and sex. Plasma proteins were analyzed with quantitative mass spectrometry. The identified and quantified proteins were compared between stroke and control patients of each sex. Proteins that showed changes in abundances in stroke patients were further analyzed with the assistance of bioinformatics tools for their known biological functions or potential implications in stroke.

A total of 128 annotated proteins were identified. Results of bioinformatic analysis of plasma proteins whose levels were increased in stroke patients showed, as expected, their association with blood coagulation and inflammation processes. Interestingly, a number of proteins showed different or even opposing changes in male and female stroke patients, notably those involved in IL-4 and IL-6 signaling, complement activation, and blood coagulation disorders. For a few proteins that were increased in female but unchanged or decreased in male stroke patients, an association with fibromuscular dysplasia was recognized.

Plasma proteins that differ in quantities between stroke patients and controls were readily detected using a simple proteomic approach. Sex-dependent changes and changes that have not been reported for African American stroke patients offer potentially novel biomarkers for stroke in this underserved population.