LC3 as a potential therapeutic target in hypoxia-induced pulmonary hypertension

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19 Scopus citations

Abstract

Recent research suggests that microtubule-associated protein 1 light chain 3B (LC3B) confers protection against hypoxia-induced pulmonary hypertension (HPH) by inhibiting proliferation of pulmonary artery (PA) wall cells. We recently demonstrated that 17β-estradiol (E2), a sex hormone with known protective properties in HPH, increases lung LC3-II expression in chronically hypoxic male Sprague-Dawley rats. Stimulatory E2 effects on LC3-II were recapitulated in isolated hypoxic (1% O2 for 48 h), but not room air-exposed primary rat PA endothelial cells (PAECs), and were accompanied by hypoxia-specific inhibitory effects on other parameters involved in proproliferative signaling (MAPK3/ERK1-MAPK1/ERK2 activation, VEGF secretion), as well as inhibitory effects on PAEC proliferation. Taken together, these results suggest that E2 mediates hypoxia-specific antiproliferative effects in PAECs, and that stimulation of autophagy may be one of the underlying mechanisms of E2-mediated protection in HPH. Viewed in the context of previously published data, these results indicate that LC3 (1) exerts protective effects in the pathogenesis of HPH, and (2) may represent a potential target for future therapeutic interventions in HPH.

Original languageEnglish (US)
Pages (from-to)1146-1147
Number of pages2
JournalAutophagy
Volume8
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • 17-beta estradiol
  • Cell proliferation
  • Estrogen
  • Hypoxia
  • MAPK1/ERK2
  • MAPK3/ERK1
  • Pulmonary artery endothelial cells
  • Pulmonary vascular remodeling

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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