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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Cerebrovascular disease; Inflammation; Native American; Oneida Nation; Proteomics; Stroke; Vascular biomarker.