The Relation between Immune Cell Mitochondrial Respiration and Brachial Artery Pulse Pressure in Humans

Abstract

Elevated pulse pressure (PP) occurs with advancing age due to stiffening of the elastic arteries and is an important risk factor for cardiovascular disease (CVD), even among normotensive adults. Mitochondrial function declines with aging and may contribute to the increase in PP through a mechanism involving oxidative stress and chronic inflammation; two important hallmarks of arterial aging. Emerging evidence indicates that mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) is negatively associated with risk factors for CVD in heart failure; however, the role of impaired mitochondrial function on cardiovascular function in healthy adults is not known. We hypothesized that mitochondrial function would be negatively associated with brachial PP. Twenty‐two healthy adults free of overt CVD (12 M/10 F; age: 56 ± 21 years; age range: 22–78 years; blood pressure, BP: 123 ± 15/72 ± 10 mmHg; PP: 51 ± 11 mmHg) were included in this analysis. PP was determined from brachial artery BP assessed in triplicate in the non‐dominant arm using an automated BP monitor. PBMCs were isolated by density dependent centrifugation and used to assess mitochondrial function by respirometry using an Agilent Seahorse XFp Analyzer. Primary outcome measures included the oxygen consumption rate (OCR) at baseline (basal respiration; BASERESP) and following three serial injections of oligomycin, FCCP and rotenone/antimycin A into the respirometer to determine maximal respiration (MAXRESP). Spare respiratory capacity (SRC), an indicator of how well the cell can respond to an increased energetic demand, ATP‐linked oxygen consumption (ATPO2), and coupling efficiency, which is how well ATPO2 is matched to BASERESP, were also measured. The associations between mitochondrial function and PP were analyzed using multi‐linear regressions correcting for age. PP was not associated with BASERESP (p=0.89, R2=0.10, β=0.01), coupling efficiency (p=0.20, R2=0.18, β= −8.5), or ATPO2 (p=0.33, R2=0.15, β= −0.10). However, PP was inversely associated with MAXRESP (p=0.05, R2=0.28, β= − 0.03) and SRC (PP; p=0.02, R2=0.33, β=−0.04). These data suggest that the impaired mitochondrial respiration may be an important contributor to CVD risk through increases in pulse pressure. Future studies should explore whether these associations are mediated by increases in oxidative stress and inflammatory cytokines.Support or Funding InformationFunding Sources: P20GM113125, K01AG054731