Altered Macrophage Polarization Induces Experimental Pulmonary Hypertension and Is Observed in Patients With Pulmonary Arterial Hypertension

Objective: To determine whether global reduction of CD68 (cluster differentiation) macrophages impacts the development experimental pulmonary arterial hypertension (PAH) and this affects balance pro- anti-inflammatory within lung. Additionally, to there is evidence an altered macrophage polarization in patients with PAH. Approach Results: Macrophage was induced mice via doxycycline-induced CD68-driven cytotoxic diphtheria toxin A chain expression (macrophage low [MacLow] mice). Chimeric were generated using bone marrow transplant. Mice phenotyped for PAH by echocardiography closed chest cardiac catheterization. Murine phenotyping performed on lungs, marrow–derived macrophages, alveolar immunohistochemical flow cytometry. Monocyte-derived isolated from healthy volunteers capacity assessed morphologically After 6 weeks depletion, male but not female MacLow developed demonstrated a requirement both recipient cause Immunohistochemical analysis lung sections imbalance M1/M2 ratio only, suggesting that may drive phenotype. also seen patient monocyte-derived following stimulation doxycycline IL (interleukin)-4, respectively. Furthermore, MacLow-derived showed characteristic differences terms their doxycycline. Conclusions: These data further highlight sex implicate immune cells into paradigm. Targeting population offer future therapeutic option.