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A Proposed Mitochondrial–Metabolic Mechanism for Initiation and Maintenance of Pulmonary Arterial Hypertension in Fawn-Hooded Rats: The Warburg Model of Pulmonary Arterial Hypertension

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Membrane Receptors, Channels and Transporters in Pulmonary Circulation

Part of the book series: Advances in Experimental Medicine and Biology ((volume 661))

Abstract

Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature that is characterized by vascular obstruction and progressive right ventricular failure. One hallmark of clinical PAH is its very poor survival, with PAH mortality rates approximating those of many malignancies. The discovery that the fawn-hooded rat strain (FHR) spontaneously develops PAH has allowed for major insights into the pathophysiology of PAH. These findings have revealed that cancer and PAH not only share a similarly poor prognosis but also demonstrate similar resistance to apoptosis and activation of cell proliferation as a major pathophysiologic mechanism. One of the causes for the resistance to apoptosis and increased proliferation of pulmonary vascular smooth muscle cells in PAH is a cancer-like metabolic shift towards a glycolytic metabolism (Warburg effect) and down-regulation of mitochondrial glucose oxidation. This book chapter will review the role of such a metabolic shift in the pathophysiology of PAH and also highlight emerging anti-proliferative PAH therapies that correct the metabolic dysregulation in PAH.

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Acknowledgments

This work is supported by the Harold Hines Jr. Chair in Medicine and NIH-RO1-HL071115.

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Authors and Affiliations

  1. Section of Cardiology, Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC6080, Chicago, IL, 60637, USA

    Jalees Rehman & Stephen L. Archer

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  1. Jalees Rehman
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  2. Stephen L. Archer
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Editors and Affiliations

  1. Departments of Medicine and Pharmacology, University of Illinois at Chicago, Chicago, 60612, USA

    Jason X. -J. Yuan

  2. Guy’s Hospital Campus, Dept. Physiology, King’s College London, London, SE1 1UL, United Kingdom

    Jeremy P. T. Ward

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Rehman, J., Archer, S.L. (2010). A Proposed Mitochondrial–Metabolic Mechanism for Initiation and Maintenance of Pulmonary Arterial Hypertension in Fawn-Hooded Rats: The Warburg Model of Pulmonary Arterial Hypertension. In: Yuan, JJ., Ward, J. (eds) Membrane Receptors, Channels and Transporters in Pulmonary Circulation. Advances in Experimental Medicine and Biology, vol 661. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-500-2_11

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