4.7 Article

Targeting Energetic Metabolism A New Frontier in the Pathogenesis and Treatment of Pulmonary Hypertension

Journal

Publisher

AMER THORACIC SOC
DOI: 10.1164/rccm.201108-1536PP

Keywords

glycolytic shift; hypoxia-inducible factor; fatty acid oxidation; right ventricular hypertrophy; pulmonary hypertension

Funding

  1. NIH [RC1HL100849, K08HL105536]
  2. Cardiovascular Medical and Research Fund
  3. Parker B. Francis Fellowship

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This perspective highlights advances in the understanding of the role of cellular metabolism in the pathogenesis of pulmonary hypertension. Insights gained in the past 20 years have revealed several similarities between the cellular processes underlying the pulmonary vascular remodeling in pulmonary hypertension and those seen in cancer processes. In line with these insights, there is increasing recognition that abnormal cellular metabolism, notably of aerobic glycolysis (the Warburg effect), the potential involvement of hypoxia-inducible factor in this process, and alterations in mitochondrial function, are key elements in the pathogenesis of this disease. The glycolytic shift may underlie the resistance to apoptosis and increased vascular cell proliferation, which are hallmarks of pulmonary hypertension. These investigations have led to novel approaches in the diagnosis and therapy of pulmonary hypertension.

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