Novel Cerebrovascular Disease Blood Biomarkers Identified by Targeted Proteomics in a High-Risk Native American Population.

Abstract

Native Americans (NAs) experience a greater prevalence of risk factors for stroke, including obesity, hypertension, and cognitive impairment than any other American racial/ethnic group. We have studied a representative NA from the Oneida Nation (NAON) of Wisconsin for these risk factors. Omics-based approaches to identify clinically relevant biomarkers may predict the molecular mechanisms, risk of cerebrovascular disease (CVD), and recovery potential in people of all cultures. We conducted a cross-sectional study on 113 adult NAONs and 17 age- and sex-matched Wisconsin general population (WGP). We used an antibody array-based targeted proteomics platform to identify plasma proteins significantly altered in NAON as compared with WGP. In NAON as compared to WGP, of 58 targeted plasma proteins, levels of 14 proteins were significantly altered. Specifically, 10 proteins including serpin E1 were significantly increased, and 4 proteins including myeloperoxidase were significantly decreased. Within NAON, leptin and angiopoietin-like 3 were significantly increased in female as compared with male subjects. Significantly increased levels of oncostatin-M, growth hormone, and chemokine C-C motif ligand 2 were seen in historically hypertensive NAON. Six proteins, including leptin, were significantly increased in NAON individuals with obesity. Increase in 3 biomarkers correlated with increasing age, increase in 6 biomarkers correlated with increasing body mass index, and an increase in 3 biomarkers correlated with increasing carotid artery total plaque area. We have identified altered blood biomarkers related to CVD in NAON for risk-stratification of CVD-related complications. Further study of these biomarkers may complement existing clinical risk factors for prevention, diagnosis, and therapy in CVD.