ArticleThe Journal of experimental medicine2021
PDGF-D activation by macrophage-derived uPA promotes AngII-induced cardiac remodeling in obese mice.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Multiple triggering mechanisms of myocardial fibrosis: Comparison and integration in different disease contexts.iScience · 2026Review
- Causal role of adipose tissue-derived adipokines in the pathogenesis of heart failure with preserved ejection fraction: experimental demonstration as the basis for clinical targeting.European heart journal · 2026Article
- Beyond Fibrinolysis: Urokinase Plasminogen Activator as an Early Regulator of Obesity.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Canonical and emerging regulatory mechanisms of tissue remodeling: shared principles across organs and therapeutic opportunities.Frontiers in immunology · 2026Review
- Article
- Central Adiposity or Hypertension: Which Drives Heart Failure With a Preserved Ejection Fraction?Journal of the American College of Cardiology · 2025Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Exploring the Impact of Platelet-Derived Growth Factor D in Pulmonary Hypertension Development.Pulmonary circulation · 2025Article
- Fetuin B Is Related to Cytokine/Chemokine and Insulin Signaling in Adipose Tissue and Plasma in Humans.The Journal of clinical endocrinology and metabolism · 2025Article
- Obesity accelerates cardiovascular ageing.European heart journal · 2025Review
- PDGF-D Promotes Epithelial-Mesenchymal Transition of Glioma Cells Through the NF-κB/NOTCH1 Pathway.Cancer medicine · 2025Article
- Complex regulation of cardiac fibrosis: insights from immune cells and signaling pathways.Journal of translational medicine · 2025Review
- Single-Cell Analysis of Subcutaneous Fat Reveals Profibrotic Cells That Correlate With Visceral Adiposity in HIV.The Journal of clinical endocrinology and metabolism · 2024Article
- Review
- The Notch-PDGFRβ axis suppresses brown adipocyte progenitor differentiation in early post-natal mice.Developmental cell · 2024Article
- PDGF-D Is Dispensable for the Development and Progression of Murine Alport Syndrome.The American journal of pathology · 2024Article
- Cardiac macrophage metabolism in health and disease.Trends in endocrinology and metabolism: TEM · 2024Review
- Inflammatory Mechanisms in Heart Failure with Preserved Ejection Fraction.Physiology (Bethesda, Md.) · 2023Review
- Central role of cardiac fibroblasts in myocardial fibrosis of diabetic cardiomyopathy.Frontiers in endocrinology · 2023Review
- Identification of the hub genes related to adipose tissue metabolism of bovine.Frontiers in veterinary science · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity-induced secretory disorder of adipose tissue-derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in angiotensin II (AngII)-infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue as well as more severe cardiac remodeling compared with control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow-specific uPA knockdown decreased active PDGF-DD levels in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte: that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice.
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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.