Abstract 15729: Reduction of CD68+ Cells Causes Spontaneous Pulmonary Arterial Hypertension in Mice

Rational: Macrophages are proposed to play an important regulatory role in the pathogenesis of pulmonary arterial hypertension (PAH) with infiltration detected around vascular lesions in patients and animal models. The exact ‘causal’ role for macrophages, and whether their presence or absence is required or sufficient for the vascular remodelling seen in PAH remains unclear. Objectives: Using a novel inducible macrophage depletion model (MacLow mouse) we aimed to determine the role of macrophages in pulmonary arterial remodeling associated with PAH. Methods and results: Macrophage depletion was induced in MacLow mice by administration of doxycycline, where macrophage-specific induction of the cytotoxic diphtheria toxin A chain is driven by the CD68 promoter. Mice were phenotyped for PAH by echocardiography, closed chest cardiac catheterization and immunohistochemistry (IHC) after 6 weeks. Interestingly male but not female MacLow mice developed a PAH phenotype compared to controls (RVSP of 66.1 mmHg vs 24....