Journal of Molecular Medicine

, Volume 88, Issue 10, pp 1003–1010 | Cite as

The role of mitochondria in pulmonary vascular remodeling

  • Peter Dromparis
  • Gopinath Sutendra
  • Evangelos D. Michelakis
Review

Abstract

Pulmonary arterial hypertension (PAH) is characterized by a hyperproliferative and anti-apoptotic diathesis within the vascular wall of the resistance pulmonary arteries, leading to vascular lumen occlusion, right ventricular failure, and death. Most current therapies show poor efficacy due to emphasis on vasodilation (rather than proliferation/apoptosis) and a lack of specificity to the pulmonary circulation. The multiple molecular abnormalities described in PAH are diverse and seemingly unrelated, calling for therapies that attack comprehensive, integrative mechanisms. Similar abnormalities also occur in cancer where a cancer-specific metabolic switch toward a non-hypoxic glycolytic phenotype is thought to be not only a result of several primary molecular or genetic abnormalities but also underlie many aspects of its resistance to apoptosis. In this paper, we review the evidence and propose that a metabolic, mitochondria-based theory can be applied in PAH. A pulmonary artery smooth muscle cell mitochondrial remodeling could integrate a number of diverse molecular abnormalities described in PAH and respond by orchestrating a switch toward a cancer-like glycolytic phenotype that drives resistance to apoptosis; via redox and calcium signals, this mitochondrial remodeling may also regulate critical transcription factors like HIF-1 and nuclear factor of activated T cells that have been described to play an important role in PAH. Because mitochondria in pulmonary arteries are quite different from mitochondria in systemic arteries, they could form the basis of relatively selective PAH therapies. This metabolic theory of PAH could facilitate the development of novel diagnostic and selective therapeutic approaches in this disease that remains deadly.

Keywords

Pulmonary arterial hypertension Cancer Metabolism Mitochondrial remodeling Apoptosis resistance 

Notes

Conflict of interest statement

The authors declare that they have no conflict of interests.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Peter Dromparis
    • 1
  • Gopinath Sutendra
    • 1
  • Evangelos D. Michelakis
    • 1
  1. 1.Pulmonary Hypertension ProgramUniversity of AlbertaEdmontonCanada

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