ArticleCirculation2010
The alternative pathway is critical for pathogenic complement activation in endotoxin- and diet-induced atherosclerosis in low-density lipoprotein receptor-deficient mice.
Article in Circulation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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32 citing papers in PubMed, 64 citations in OpenAlex.
- A zebrafish model for uremic toxicity: role of the complement pathway.Blood purification · 2013Trial
- Gut Microbiota and Atherosclerosis: Integrative Multi-Omics and Mechanistic Insights.Current atherosclerosis reports · 2025Review
- Complement C3 in panvascular disease: a central integrator of immune signaling and vascular remodeling.Clinical science (London, England : 1979) · 2025Review
- The role of complement C1q in atrial fibrillation: a marker for disease progression and surgical outcomes.Frontiers in cardiovascular medicine · 2025Article
- The association between serum lipids at diagnosis and renal outcome in microscopic polyangiitis patients.PeerJ · 2025Article
- Canonical and non-canonical roles of complement in atherosclerosis.Nature reviews. Cardiology · 2024Review
- Article
- Zebrafish as a Model of Cardiac Pathology and Toxicity: Spotlight on Uremic Toxins.International journal of molecular sciences · 2023Review
- Deficiency of CFB attenuates renal tubulointerstitial damage by inhibiting ceramide synthesis in diabetic kidney disease.JCI insight · 2022Article
- Article
- Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery.Antioxidants (Basel, Switzerland) · 2022Article
- Article
- Metformin directly suppresses atherosclerosis in normoglycaemic mice via haematopoietic adenosine monophosphate-activated protein kinase.Cardiovascular research · 2021Article
- Anti-inflammatory Action of Statins in Cardiovascular Disease: the Role of Inflammasome and Toll-Like Receptor Pathways.Clinical reviews in allergy & immunology · 2021Review
- Hematoma Resolution In Vivo Is Directed by Activating Transcription Factor 1.Circulation research · 2020Article
- Functional Evaluation of AMD-Associated Risk Variants of Complement Factor B.Investigative ophthalmology & visual science · 2020Article
- Amitriptyline inhibits nonalcoholic steatohepatitis and atherosclerosis induced by high-fat diet and LPS through modulation of sphingolipid metabolism.American journal of physiology. Endocrinology and metabolism · 2020Article
- Function and Dysfunction of Complement Factor H During Formation of Lipid-Rich Deposits.Frontiers in immunology · 2020Review
- Gut microbiome and cardiometabolic risk.Reviews in endocrine & metabolic disorders · 2019Review
- Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe early components of the classical and lectin complement pathways have been shown to protect low-density lipoprotein receptor-deficient mice (Ldlr(-/-)) from early atherogenesis. However, the role of the alternative pathway remained unknown, and that was investigated in this study. METHODS AND
resultsMice lacking factor B (Bf(-/-)), the initiator of the alternative pathway, were crossed with Ldlr(-/-) mice and studied under different proatherogenic conditions. There was no statistically significant difference in lipid profiles or atherosclerotic lesion development between Bf(-/-)/Ldlr(-/-) and Ldlr(-/-) mice fed a low-fat diet. However, in these groups, administration of bacterial lipopolysaccharide led to a significant increase in atherosclerosis only in Ldlr(-/-) and not in Bf(-/-)/Ldlr(-/-) mice, indicating that the alternative pathway is necessary for endotoxin-mediated atherogenesis. Bf(-/-)/Ldlr(-/-) mice also had significantly decreased cross-sectional aortic root lesion fraction area and reduced lesion complexity compared with Ldlr(-/-) animals after a 12-week period of high-fat diet, although this was also accompanied by reduced levels of serum cholesterol. Under both experimental conditions, the atherosclerotic changes in the Bf(-/-)/Ldlr(-/-) mice were accompanied by a marked reduction in complement activation in the circulation and in atherosclerotic plaques, with no statistically significant differences in immunoglobulin G deposition or in the serum antibody response to oxidized low-density lipoprotein.
conclusionsThese data demonstrate that amplification of complement activation by the alternative pathway in response to lipopolysaccharide or high-fat diet plays a proatherogenic role.
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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.