ArticlePloS one2011
Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 65 citations in OpenAlex.
- Plasma Proteomic Study in Pulmonary Arterial Hypertension Associated with Congenital Heart Diseases.Scientific reports · 2016Trial
- Contribution of omics to the pathophysiology of diaphragmatic hernias: a narrative review.European journal of pediatrics · 2025Review
- Identification of serum C4BPA as a potential diagnostic marker of right ventricular remodelling via proteomic analysis.ESC heart failure · 2025Article
- Complement Immune System in Pulmonary Hypertension-Cooperating Roles of Circadian Rhythmicity in Complement-Mediated Vascular Pathology.International journal of molecular sciences · 2024Review
- Selection and Gene Duplication Associated With High-Elevation Diversification in Pristimantis, the Largest Terrestrial Vertebrate Genus.Genome biology and evolution · 2024Article
- A novel complement C3 inhibitor CP40-KK protects against experimental pulmonary arterial hypertension via an inflammasome NLRP3 associated pathway.Journal of translational medicine · 2024Article
- Article
- Beneficial effects of Panax notoginseng (Burkill) F. H. Chen flower saponins in rats with metabolic hypertension by inhibiting the activation of the renin-angiotensin-aldosterone system through complement 3.BMC complementary medicine and therapies · 2023Article
- C3-dependent effector functions of complement.Immunological reviews · 2023Review
- Chronic hypoxia disrupts T regulatory cell phenotype contributing to the emergence of exTreg-TFrontiers in physiology · 2023Article
- Hemodynamically Unloading the Distal Pulmonary Circulation in Pulmonary Hypertension: A Modeling Study.Journal of biomechanical engineering · 2022Article
- Plasma proteoglycan prolargin in diagnosis and differentiation of pulmonary arterial hypertension.ESC heart failure · 2021Article
- Platelet activation contributes to hypoxia-induced inflammation.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Effect of EZH2 on pulmonary artery smooth muscle cell migration in pulmonary hypertension.Molecular medicine reports · 2021Article
- Autoimmunity in Pulmonary Arterial Hypertension: Evidence for Local Immunoglobulin Production.Frontiers in cardiovascular medicine · 2021Review
- Review
- A proteome signature of umbilical cord serum associated with congenital diaphragmatic hernia.Nagoya journal of medical science · 2020Article
- Inflammation, immunity, and vascular remodeling in pulmonary hypertension; Evidence for complement involvement?Global cardiology science & practice · 2020Review
- Immunoglobulin-driven Complement Activation Regulates Proinflammatory Remodeling in Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2020Article
- Adverse effects of BMPR2 suppression in macrophages in animal models of pulmonary hypertension.Pulmonary circulation · 2019Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEvidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension. METHODOLOGY/PRINCIPAL
findingsImmunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.
conclusionsHerein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.
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