PerspectivePulmonary Hypertension

PPARγ Activation: A Potential Treatment For Pulmonary Hypertension

Science Translational Medicine  23 Dec 2009:
Vol. 1, Issue 12, pp. 12ps14
DOI: 10.1126/scitranslmed.3000267

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Abstract

The pathobiology of pulmonary arterial hypertension (PAH) involves multiple molecular pathways and environmental modifiers and is characterized by progressive obliteration of pulmonary arterioles, leading to increased pulmonary vascular resistance (PVR), right heart failure, and death in ≈40 to 60% of patients 5 years after diagnosis. There is emerging evidence that many key genes involved in PAH development are targets of the insulin-sensitizing transcription factor peroxisome proliferator–activated receptor γ (PPARγ), and that pharmacological PPARγ activation would lead to their beneficial induction or repression and subsequent antiproliferative, anti-inflammatory, proapoptotic, and direct vasodilatory effects in the vasculature. PPARγ acts downstream of bone morphogenetic protein receptor II (BMP-RII), which is the cell surface receptor that is mutated or dysfunctional in many forms of PAH. Because our recent clinical observations indicate that insulin resistance may be an environmental risk factor or disease modifier (“second hit”), we suggest that PPARγ-activating agents might be beneficial in the future treatment of both insulin-resistant and insulin-sensitive PAH patients with or without BMP-RII mutations.

Footnotes

  • Citation: G. Hansmann, R. T. Zamanian, PPARγ activation: A potential treatment for pulmonary hypertension. Sci. Transl. Med. 1, 12ps14 (2009).

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