Abstract 16821: Reductions in Vascular Function Correlate with Age in a Novel Non-Human Primate Model for Assessment of Vascular Health

Abstract

Background: Non human primates develop cardiovascular disease over decades. Whether the progression of vascular dysfunction with age is like that observed in humans is unclear. We hypothesize that, like humans, monkeys show age-related reductions in flow-mediated dilation (FMD, an index of endothelium-dependent vascular reactivity) and increases in pulse-wave velocity (PWV, an index of aortic stiffness). We also explored a potential relationship between the age-related vascular effects and circulating biomarkers of endothelial health, endothelial microparticles (EMP) and endothelial progenitor cells (EPC). Methods and Results: In M. fascicularis monkeys (N=21, 14 males and 7 females, 6 to 25 years of age), blood was sampled for EPC and EMP that were measured using flow cytometry. Monkeys were then sedated (midazolam + torbugesic) and baseline femoral artery diameter (4mm segment) was measured by ultrasonography. FMD was calculated as the peak %change from baseline diameter following a 5-minute cessation of blood flow below the knee. PWV was calculated using a modified SphygmoCor program and pulse waves from the radial and femoral arteries. FMD and PWV ranged from 6 to 33% and from 3 to 7 m/s, respectively, and multiple samplings showed high reproducibility up to 4 months (inter-assay variation <5%). FMD negatively (r=-0.94, p<0.0001), while PWV positively (r=0.60, p<0.002) correlated with age in these monkeys. Numbers of EPC (CD45- CD31+ CD34+ VEGFR2+) and EMP [CD45- CD42a- CD54(ICAM-1)+, CD45- CD42a- CD105(endoglin)+, and CD45- CD42a- CD144(VE-cadherin)+] were highly variable between individuals. Neither the EPC nor any of the EMPs significantly correlated with the age or age-related changes in FMD or PWV. Significance = p<0.05. Conclusion: For the first time in non-human primates, we established two non-invasive, clinically-relevant assessments of vascular function, FMD and PWV. Like humans, monkeys show age-related reductions in endothelium-dependent vascular reactivity and increases in aortic stiffness. The circulating numbers of EMP and EPC, independent of the chronic, age-related changes in FMD and PWV, may better serve as biomarkers of acute changes in vascular health associated with disease or therapeutic interventions.