Elevated LDL-C, high blood pressure, and low peak V ˙ O2 associate with platelet mitochondria function in children-The Arkansas Active Kids Study

Abstract

Purpose: To evaluate the association of platelet (PL) mitochondria respiration with markers of cardiovascular health in children ages 7-10 years. Methods: PL mitochondrial respiration (n = 91) was assessed by high resolution respirometry (HRR): Routine (R) respiration, complex (C) I linked respiration (CI), and maximal uncoupled electron transport capacity of CII (CII_E) were measured. The respiratory control ratio (RCR) was calculated as the ratio of maximal oxidative phosphorylation capacity of CI and CI leak respiration (P_CI/L_CI). Peak $\dot{V}$ O₂ (incremental bike test) and body composition (dual-energy X-ray absorptiometry) were measured. Multiple generalized linear regression analysis was used to model the association of measures by HRR with variables of interest: adiposity, low-density lipoprotein (LDL-C) and triglyceride (TG) status (normal vs. elevated) HOMA2-IR, blood pressure status (normal vs. high), and demographics. Results: R and CI-linked respiration positively associated with adiposity, high blood pressure (HBP), and peak $\dot{V}$ O₂. R and CI-linked respiration had inverse association with age and elevated LDL-C. CII_E was higher in children with elevated LDL-C (log-β = -0.54, p = 0.010). HBP and peak $\dot{V}$ O₂ interacted in relation to RCR (log-β = -0.01, p = 0.028). Specifically, RCR was lowest among children with HBP and low aerobic capacity (i.e., mean peak $\dot{V}$ O₂ -1SD). HOMA2-IR did not associate with measures of PL mitochondria respiration. Conclusion: In PL, R and CI-linked mitochondrial respiration directly associate with adiposity, peak $\dot{V}$ O₂ and HBP. Elevated LDL-C associates with lower CI-linked respiration which is compensated by increasing CII respiration. PL bioenergetics phenotypes in children associate with whole-body metabolic health status.

Keywords: aerobic capacity; blood platelets; body composition; cardiometabolic risk (factors); mitochondria.

FIGURE 1

Simplified schematic representation of the mitochondrial electron transport chain.

FIGURE 2

Fitted plot showing the association of CI maximal oxidative phosphorylation capacity plus 95% confidence intervals with fat mass index z-score (x-axis), LDL-cholesterol status, and blood pressure status (HBP = high blood pressure).

FIGURE 3

Fitted plot showing the interaction between peak $\dot{\mathrm{V}}$ O₂ and high blood pressure in relation to RCR. Peak $\dot{\mathrm{V}}$ O₂—level groups were created using the group average ± 1SD.