Type 2 Diabetes and Older Age Contribute to Elevated Plasma Microparticle Concentrations

Abstract

Endothelialmicroparticles (MPs) are small particles shed from the endothelium in responseto cellular activation and apoptosis and may serve as biomarkers of cardiovascular(CV) risk. The purpose of this study was to determine the effects of age, chronic stroke and type 2 diabetes mellitus (T2DM) on CD31+/CD42b−, CD62E+ andCD34+ MPs as biomarkers of endothelial apoptosis, activation and stress, respectively. Fasting blood samples were obtained from young (18–39 years old)and older (50–75 years old) healthy adults, as well as older adults with chronicstroke or T2DM (n=17/group). Cell‐free plasma was separated from fasting bloodsamples and incubated with antibodies against CD31, CD42b, CD62E or CD34 and MPconcentrations normalized to absolute number of events and quantified using anLSR II flow cytometer. Results showed that CD31+/CD42b− MP concentration was relatively low in young adults (36 ± 8 particles/μL) and not different in healthy older adults (71 ± 20 particles/μL P>0.05); however, CD31+/CD42b− MP concentrations from chronic stroke subjects were 124% higher than younger adults. Additionally, T2DM subjects had 145% and 107% greater CD31+/CD42b−MP concentrations than healthy young and olderadults, respectively (P<0.05 for both). Compared to young adults (211 ± 42 particles/μL), CD62E+ MP concentrations were significantly higher in all oldergroups (91%, 122% and 151%, in healthy, chronic stroke and T2DM subjects. respectively), with an additional effect of T2DM compared to healthy older adults (P<0.05 for all). Similarly, there was an effect of age on CD34+ MP concentrations, with healthy older adults, chronic stroke, and T2DM subjects having significantly higher CD34+ MP concentrations (67%, 46% and 90%, respectively; P<0.05 for all) compared to healthy younger individuals (20 ± 2 particles/μL). Because 41% of stroke subjects also had T2DM, we conducted analyses to distinguish the effects of T2DM and stroke in these participants. The diabetic stroke subjects had ~100% higher CD31+/CD42b− and CD62E+ MP concentrations compared to non‐diabetic stroke, whereas CD34+ MPs did not differ between diabetic and non‐diabetic stroke subjects. When diabetic subjects were removed from the stroke group and compared to the T2DM group there were 96% higher CD31+/CD42b− and 91% higher CD62E+ MP concentrations in the T2DM group (P<0.05 for each) and MP levels in the non‐diabetic stroke group did not differ from healthy olderadults. Collectively, these results suggest that elevated concentrations of CD31+/CD42b− and CD62E+ MPs are driven by older age with an additional effect of T2DM but not stroke; whereas older age alone causes elevations in CD34+ MPs. Our findings indicate the potential for MPs as a novel biomarker for assessing endothelial health and CV risk in aging populations.Support or Funding InformationVeteransAffairs Maryland Exercise and Robotics Center of Excellence (MERCE)K23‐ AG040775(NIH and the American Federation for Aging Research);I01‐CX000730(Department of Veterans Affairs); Baltimore Veterans Affairs GeriatricResearch, Education and Clinical Center (GRECC),CareerDevelopment Award Number IK2 RX‐000944 from the United States (U.S) Department of Veterans Affairs Rehabilitation R&D (Rehab RD) ServiceThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.