Macrophage-derived PDGF-B induces muscularization in murine and human pulmonary hypertension

摘要: Excess macrophages and smooth muscle cells (SMCs) characterize many cardiovascular diseases, but crosstalk between these cell types is poorly defined. Pulmonary hypertension (PH) a lethal disease in which lung arteriole SMCs proliferate migrate, coating the normally unmuscularized distal arteriole. We hypothesized that increased macrophage platelet-derived growth factor-B (PDGF-B) induces pathological SMC burden PH. Our results indicate clodronate attenuates hypoxia-induced accumulation, muscularization, PH, right ventricle hypertrophy (RVH). With hypoxia exposure, Pdgfb mRNA was upregulated mice, LysM‑Cre mice carrying floxed alleles for hypoxia-inducible factor 1a, 2a, or had reduced were protected against muscularization Conversely, von-Hippel Lindaufl/fl Hifa developed RVH normoxia. Similarly, from human idiopathic systemic sclerosis-induced pulmonary arterial patients, macrophage-conditioned medium patients proliferation migration via PDGF-B. Finally, orotracheal administration of nanoparticles loaded with siRNA specifically prevented RVH. Thus, macrophage-derived PDGF-B critical expansion nanoparticle-mediated inhibition has profound implications as an interventional strategy