title: LC3 as a potential therapeutic target in hypoxia-induced pulmonary hypertension.
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% O 2 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.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care, Occupational and Sleep Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. tlahm@iupui.edu
authors.forename: Tim
authors.initials: T
authors.lastname: Lahm
authors.forename: Irina
authors.initials: I
authors.lastname: Petrache
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D011960:Receptors, Estrogen / Q000187:drug effects*
chemical_list: D011960:Receptors, Estrogen; D004958:Estradiol