Translocation of bone marrow‐derived cells contribute to PVN neuroinflammation in hypoxia‐induced PH

Background Pulmonary hypertension is a devastating disease characterized by elevated pressures in the pulmonary arterial circulation leading to right heart failure. Our previous studies have indicated that PH is not only a lung disease but a systemic disease and an altered brain‐gut‐lung axis is involved in the pathogenesis and progression of the disease. Aim This study was designed to explore the contribution of bone marrow‐derived cells to neuroinflammation in hypoxia‐induced PH model Methods Green fluorescent protein (GFP) bone marrow (BM) chimeric mice (C57BL6 strain) were generated by transplanting GFP BM cells into lethally irradiated WT mice. 3 months later, subjects were exposed to chronic hypoxia (10%O2) or Normoxia for 4 weeks in a ventilated chamber (n=6–10/group). An Millar pressure catheter was used to measure pulmonary hemodynamics, microglial cells specifically stained with Iba1 and migration of BM‐derived cells were also evaluated. Results Hypoxia induced an increase in right ventricular (RV) systolic pressure (RVSP: Normoxia (N):22.12 ± 2 mmHg vs Hypoxia (H):32.7 ± 2, p<0.001) and RV hypertrophy (RVH:N: 0.139 ± 0.09 vs H:0.201 ± 0.01, p<0.001) in chimera mice. Besides the lungs, PH also induced an increase in BM‐derived cells in the paraventricular nucleus of hypothalamus (PVN) (N 2.599:±1VsH:10.29 ±2, p<0.001) and the jejunum (N 11.08:±0.26VsH:12.65 ±0.35, p<0.001). Conclusion Exposure of chimeric mice with GFP bone marrow cells to chronic hypoxia illustrate the translocation of these cells into organs we have recently described to be associated with PH; the brain and gut. This data indicates that BM‐ derived cells may contribute to the dysfunctional brain‐gut‐lung axis observed in PH. Support or Funding Information This research is supported by NIH grant HL102033. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .