Platelets from pulmonary hypertension patients show increased mitochondrial reserve capacity
Quyen L. Nguyen, Catherine Corey, Pamela White, Annie Watson, Mark T. Gladwin, Marc A. Simon, Sruti Shiva
Quyen L. Nguyen, Catherine Corey, Pamela White, Annie Watson, Mark T. Gladwin, Marc A. Simon, Sruti Shiva
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Research Article Pulmonology

Platelets from pulmonary hypertension patients show increased mitochondrial reserve capacity

Abstract

Accumulating evidence suggests that altered cellular metabolism is systemic in pulmonary hypertension (PH) and central to disease pathogenesis. However, bioenergetic changes in PH patients and their association with disease severity remain unclear. Here, we hypothesize that alteration in bioenergetic function is present in platelets from PH patients and correlates with clinical parameters of PH. Platelets isolated from controls and PH patients (n = 28) were subjected to extracellular flux analysis to determine oxygen consumption and glycolytic rates. Platelets from PH patients showed greater glycolytic rates than controls. Surprisingly, this was accompanied by significant increases in the maximal capacity for oxygen consumption, leading to enhanced respiratory reserve capacity in PH platelets. This increased platelet reserve capacity correlated with mean pulmonary artery pressure, pulmonary vascular resistance, and right ventricular stroke work index in PH patients and was abolished by the inhibition of fatty acid oxidation (FAO). Consistent with a shift to FAO, PH platelets showed augmented enzymatic activity of carnitine palmitoyltransferase-1 and electron transport chain complex II. These data extend the observation of a metabolic alteration in PH from the pulmonary vascular axis to the hematologic compartment and suggest that measurement of platelet bioenergetics is potentially useful in assessment of disease progression and severity.

Authors

Quyen L. Nguyen, Catherine Corey, Pamela White, Annie Watson, Mark T. Gladwin, Marc A. Simon, Sruti Shiva

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Figure 1

PH platelets have altered bioenergetics.

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PH platelets have altered bioenergetics. (A) Representative ECAR tracing...
(A) Representative ECAR tracing in platelets from a control subject and a PH patient. (B) Basal glycolytic rate in control and PH subjects (n = 28/group). Data are mean ± SEM. (C) Representative platelet OCR profiles from 1 healthy control subject and a patient with PH. (D) Quantification of individual components of the platelet OCR profile in control and PH subjects (n = 28/group). Boxes show the 25%–75% percentile; whiskers show the minimum-maximum; lines represent the median; + represents the mean. (E) Mitochondrial superoxide production, measured by MitoSOX fluorescence, in control (n = 28) and PH (n = 19) platelets. Data are mean ± SEM. (F) Percent activated platelets, as measured by CD62 positivity, in control (n = 19) and PH (n = 16) subjects. Data are mean ± SEM. Unpaired 2-tailed t test was used to compare groups. *P < 0.01. Oligo, oligomycin; rote, rotenone.