PT - JOURNAL ARTICLE AU - Tanba, Carl AU - Qi, Guanming AU - Warburton, Rod AU - Penumatsa, Krishna AU - Toksoz, Deniz AU - Wilson, Jamie AU - Farber, Harrison AU - Hill, Nicholas AU - Preston, Ioana TI - Relationship between Galectin-3 and mineralocorticoid receptor in pulmonary hypertension AID - 10.1183/13993003.congress-2020.1484 DP - 2020 Sep 07 TA - European Respiratory Journal PG - 1484 VI - 56 IP - suppl 64 4099 - http://erj.ersjournals.com/content/56/suppl_64/1484.short 4100 - http://erj.ersjournals.com/content/56/suppl_64/1484.full SO - Eur Respir J2020 Sep 07; 56 AB - Background: Galectin-3 (Gal-3), a macrophage receptor, promotes experimental pulmonary arterial hypertension (PAH); however it has not been studied in human PAH. Mineralocorticoid receptor (MR) activates macrophages and has been implicated in PAH.Objectives: Investigate the relationship between Gal-3 and MR in human and experimental PAH.Methods: Tufts PAH registry included 109 idiopathic and connective tissue disease-PAH patients (IPAH, CTD-PAH), and 39 controls. Mice with selective MR deletion in myeloid cells were exposed to sugen/hypoxia PH vs. normoxia and compared with controls. A group of PH mice was treated with spironolactone (SP) vs. controls. Lung inflammation was assessed via qPCR and western blot. Gal-3 mRNA and protein were measured in lung tissue and in cultured peritoneal macrophages from myeloid-MR KO mice and controls. Gal-3 levels were measured from human and mouse blood and human and mouse lungs were stained for Gal-3 expression.Results: PAH patients had elevated plasma Gal-3 levels vs. controls [11.1 (7.8-17) vs. 9.4 (6.6-11.35) ng/ml, median, 25-75%CI] and increased lung staining for Gal-3 positive cells. Serum Gal-3 levels were increased in PH mice and reduced by SP (P<0.01). PH mouse lungs and increased Gal-3 positive cells and this was attenuated in myeloid-MR KO mice (P<0.01). TNF-alpha mRNA was increased in PH lung mice and attenuated in myeloid-MR KOs (P<0.01). In mouse peritoneal macrophages, Gal-3 mRNA and protein expression were attenuated in myeloid-MR KO mice vs. controls (P<0.01).Conclusion: Gal-3 levels are elevated in human and experimental PAH. In experimental PH, Gal-3 is driven by macrophage MR and both are associated with increased lung inflammation.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1484.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).