HIF-1 α-L-PGDS-PPARγ regulates hypoxia-induced ANP secretion in beating rat atria

Publication date: Available online 26 December 2017 Source:Prostaglandins & Other Lipid Mediators Author(s): Xiang Li, Ying Zhang, Bo Zhang, Xia Liu, Lan Hong, Li-ping Liu, Cheng-zhe Wu, Xun Cui Lipocalin-type prostaglandin D synthase (L-PGDS) and peroxisome proliferator activated receptor γ (PPARγ) play important roles in cardiovascular diseases. Nevertheless, effects of hypoxia-inducible factor 1α (HIF-1α) on L-PGDS and PPARγ protein levels and its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion are unclear. In perfused beating rat atria, we observed that hypoxia significantly increased HIF-1α protein levels and stimulated ANP secretion, while upregulating L-PGDS. Hypoxia-induced ANP secretion was clearly attenuated by HIF-1α antagonist 2-methoxyestradiol, downregulating both HIF-1α and L-PGDS protein levels. It was also attenuated by L-PGDS antagonists, AT-56 and HQL-49, downregulating L-PGDS protein levels. In addition, hypoxia-induced ANP secretion was accompanied by increased PPARγ protein levels and was strongly attenuated by PPARγ antagonist GW9662. Hypoxia-induced increase in atrial PPARγ protein levels were dramatically inhibited by both 2-methoxyestradiol and AT-56. These results indicated that hypoxia promotes ANP secretion, at least in part, by activating HIF-1α-L-PGDS-PPARγ signaling in beating rat atria.
Source: Prostaglandins and Other Lipid Mediators - Category: Lipidology Source Type: research