ArticleJCI insight2021
Macrophage-derived PDGF-B induces muscularization in murine and human pulmonary hypertension.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 65 citations in OpenAlex.
- Macrophages Contribute to Pulmonary Hypertension Associated With Sickle Cell Disease.Pulmonary circulation · 2026Article
- The Role of Platelets in Pulmonary Hypertension: From Activation to Pulmonary Vascular Remodeling-A Review Article.Biomedicines · 2026Review
- From nanotechnology to immunomodulation: emerging strategies targeting macrophages in high altitude pulmonary hypertension.Journal of nanobiotechnology · 2026Review
- Lactate metabolism and lactylation: Therapeutic and pre-clinical implications in neovascularization in peripheral artery disease.Journal of pharmaceutical analysis · 2026Review
- Roles of the Altitude-Adapted Immune Microenvironment in Pulmonary Vascular Remodeling in High-Altitude Pulmonary Hypertension: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Pericytes and Lung Vascular Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Article
- Nobiletin alleviates hypoxia-induced pulmonary hypertension by inhibiting calcium-sensing receptor.Journal of natural medicines · 2025Article
- Cellular determinants influence the red blood cell adsorption efficiency of poly(amine-Science advances · 2025Article
- Roles of PDGF/PDGFR signaling in various organs.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- Niclosamide modulates phenotypic switch and inflammatory responses in human pulmonary arterial smooth muscle cells.Molecular and cellular biochemistry · 2025Article
- Fundamental and Targeted Approaches in Pulmonary Arterial Hypertension Treatment.Pharmaceutics · 2025Review
- Impact of sodium-glucose cotransporter-2 inhibitors on pulmonary vascular cell function and arterial remodeling.World journal of cardiology · 2025Review
- Macrophage-driven immunopathology in pulmonary arterial hypertension: from mechanisms to targeted therapies.Frontiers in immunology · 2025Review
- Biomarkers in COPD-Associated PH/CCP: Circulating Molecules and Cell-Intrinsic Marker.International journal of chronic obstructive pulmonary disease · 2025Review
- The Role of Ion Channels in Pulmonary Hypertension: A Review.Pulmonary circulation · 2025Review
- Redistribution of SOD3 expression due to R213G polymorphism affects pulmonary interstitial macrophage reprogramming in response to hypoxia.Physiological genomics · 2024Article
- Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biological research · 2024Review
- Endothelial HIFα/PDGF-B to smooth muscle Beclin1 signaling sustains pathological muscularization in pulmonary hypertension.JCI insight · 2024Article
- Novel insights and new therapeutic potentials for macrophages in pulmonary hypertension.Respiratory research · 2024Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Excess macrophages and smooth muscle cells (SMCs) characterize many cardiovascular diseases, but crosstalk between these cell types is poorly defined. Pulmonary hypertension (PH) is a lethal disease in which lung arteriole SMCs proliferate and migrate, coating the normally unmuscularized distal arteriole. We hypothesized that increased macrophage platelet-derived growth factor-B (PDGF-B) induces pathological SMC burden in PH. Our results indicate that clodronate attenuates hypoxia-induced macrophage accumulation, distal muscularization, PH, and right ventricle hypertrophy (RVH). With hypoxia exposure, macrophage Pdgfb mRNA was upregulated in mice, and LysM‑Cre mice carrying floxed alleles for hypoxia-inducible factor 1a, hypoxia-inducible factor 2a, or Pdgfb had reduced macrophage Pdgfb and were protected against distal muscularization and PH. Conversely, LysM‑Cre von-Hippel Lindaufl/fl mice had increased macrophage Hifa and Pdgfb and developed distal muscularization, PH, and RVH in normoxia. Similarly, Pdgfb was upregulated in macrophages from human idiopathic or systemic sclerosis-induced pulmonary arterial hypertension patients, and macrophage-conditioned medium from these patients increased SMC proliferation and migration via PDGF-B. Finally, in mice, orotracheal administration of nanoparticles loaded with Pdgfb siRNA specifically reduced lung macrophage Pdgfb and prevented hypoxia-induced distal muscularization, PH, and RVH. Thus, macrophage-derived PDGF-B is critical for pathological SMC expansion in PH, and nanoparticle-mediated inhibition of lung macrophage PDGF-B has profound implications as an interventional strategy for PH.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.