Figure 1. Potential role of autophagy in attenuation of hypoxia-induced pulmonary hypertension (HPH). Lack of increase or insufficient increase in LC3 in HPH may allow for pulmonary artery endothelial cell (PAEC) activation and proliferation with subsequent hypoxic pulmonary vascular remodeling. PAECs play a critical role in HPH development by secreting growth factors and pro-inflammatory cytokines that further stimulate PA smooth muscle cell proliferation and recruitment of inflammatory as well as progenitor cells. Hypoxia-specific stimulatory effects of 17β-estradiol (E2) on autophagy may attenuate PAEC activation and proliferation, thereby contributing to attenuated hypoxic pulmonary vascular remodeling. Note that, in addition to autophagy of PAECs, autophagy of PA smooth muscle cells may also represent a therapeutic target in HPH. Similar effects may be observed with other inducers of autophagy (e.g., rapamycin).