University of Pittsburgh

Platelet Bioenergetics: from marker to mechanism in vascular disease

Accumulating studies demonstrate that mitochondrial function is central to determining the susceptibility to, and prognosis of numerous diseases across all organ systems. Despite this recognition, mitochondrial function remains poorly characterized in humans primarily due to the invasiveness of obtaining viable tissue for mitochondrial studies. Here we present methodology for the measurement of circulating platelets, which can be obtained by minimally invasive methodology and utilized as a biomarker of systemic bioenergetic function in human populations. We validate this methodology in healthy subjects and apply this methodology to a number of human disease populations. This talk will focus particularly on a “bioenergetic screen” performed in a population of subjects with Sickle Cell Disease. We demonstrate that platelet mitochondria isolated from patients with Sickle Cell Disease show a significant inhibition of the mitochondrial ATP Synthase which leads to the generation of significantly greater concentrations of reactive oxygen species than healthy African American subjects. Further, we show that this bioenergetic dysfunction is secondary to hemolysis and contributes to increased platelet thrombotic and inflammatory activation observed in this patient population. Implications of altered platelet bioenergetics will be discussed in the context of the pathogenesis and therapeutics for sickle cell disease as well as other vascular pathologies.

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Host: Ivet Bahar