title: 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.affiliation: Division of Pulmonary Allergy and Critical Care Medicine.|Vascular Medicine Institute.
authors.forename: Quyen L
authors.initials: QL
authors.lastname: Nguyen
authors.affiliation: Vascular Medicine Institute.
authors.forename: Catherine
authors.initials: C
authors.lastname: Corey
authors.affiliation: Division of Cardiology.
authors.forename: Pamela
authors.initials: P
authors.lastname: White
authors.affiliation: Division of Cardiology.
authors.forename: Annie
authors.initials: A
authors.lastname: Watson
authors.affiliation: Division of Pulmonary Allergy and Critical Care Medicine.|Vascular Medicine Institute.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.affiliation: Vascular Medicine Institute.|Division of Cardiology.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Simon
authors.affiliation: Vascular Medicine Institute.|Department of Pharmacology and Chemical Biology.|Center for Metabolism and Mitochondrial Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Sruti
authors.initials: S
authors.lastname: Shiva
mesh_terms: D001792:Blood Platelets / Q000502:physiology*; D004734:Energy Metabolism; D005260:Female; D006019:Glycolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption