ArticleScientific reports2019
Dysfunctional high-density lipoprotein activates toll-like receptors via serum amyloid A in vascular smooth muscle cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Regulatory Bottlenecks Linking HDL Dysfunction, Inflammation, and Oxidative Stress: A Petri Net-Based Systems Analysis.International journal of molecular sciences · 2026Article
- Profiling Cardiovascular Disease-Associated Changes in the Composition of High-Density Lipoprotein Particles.Cardiovascular drugs and therapy · 2026Review
- Serum amyloid A in HFpEF and cardiometabolic diseases.Basic research in cardiology · 2026Review
- Serum Amyloid A (SAA) and Its Interaction with High-Density Lipoprotein Cholesterol (HDL-C): A Comprehensive Review.International journal of molecular sciences · 2025Review
- Increased expression of Toll-like receptors and associated alarmins in temporal arteries of patients with giant cell arteritis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Serum amyloid A: multifaceted roles in inflammation and cellular interactions.Immunologic research · 2025Review
- Post-translational modifications in kidney diseases and associated cardiovascular risk.Nature reviews. Nephrology · 2024Review
- Utilizing procalcitonin, C-reactive protein, and serum amyloid A in combination for diagnosing sepsis due to urinary tract infection.International urology and nephrology · 2024Article
- Article
- Alterations of HDL's to piHDL's Proteome in Patients with Chronic Inflammatory Diseases, and HDL-Targeted Therapies.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Analytical performance of a canine ELISA monocyte chemoattractant protein-1 assay for use in cats and evaluation of circulating levels in normal weight and obese cats.Acta veterinaria Scandinavica · 2022Article
- Apolipoprotein Signature of HDL and LDL from Atherosclerotic Patients in Relation with Carotid Plaque Typology: A Preliminary Report.Biomedicines · 2021Article
- Lipoproteins and fatty acids in chronic kidney disease: molecular and metabolic alterations.Nature reviews. Nephrology · 2021Review
- Review
- Vascular Stress Signaling in Hypertension.Circulation research · 2021Review
- Long-Term Treatment of Azathioprine in Rats Induces Vessel Mineralization.Biomedicines · 2021Article
- Stressor-Induced "Inflammaging" of Vascular Smooth Muscle Cells via Nlrp3-Mediated Pro-inflammatory Auto-Loop.Frontiers in cardiovascular medicine · 2021Article
- High-Density Lipoprotein Modifications: A Pathological Consequence or Cause of Disease Progression?Biomedicines · 2020Review
- High-Density Lipoprotein (HDL) Inhibits Serum Amyloid A (SAA)-Induced Vascular and Renal Dysfunctions in Apolipoprotein E-Deficient Mice.International journal of molecular sciences · 2020Article
- Role of serum amyloid A in atherosclerosis.Current opinion in lipidology · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serum amyloid A (SAA) is an uremic toxin and acute phase protein. It accumulates under inflammatory conditions associated with high cardiovascular morbidity and mortality in patients with sepsis or end-stage renal disease (ESRD). SAA is an apolipoprotein of the high-density lipoprotein (HDL). SAA accumulation turns HDL from an anti-inflammatory to a pro-inflammatory particle. SAA activates monocyte chemoattractant protein-1 (MCP-1) in vascular smooth muscle cells. However, the SAA receptor-mediated signaling pathway in vascular cells is poorly understood. Therefore, the SAA-mediated signaling pathway for MCP-1 production was investigated in this study. The SAA-induced MCP-1 production is dependent on the activation of TLR2 and TLR4 as determined by studies with specific receptor antagonists and agonists or siRNA approach. Experiments were confirmed in tissues from TLR2 knockout, TLR4 deficient and TLR2 knock-out/TLR4 deficient mice. The intracellular signaling pathway is IκBα and subsequently NFκB dependent. The MCP-1 production induced by SAA-enriched HDL and HDL isolated from septic patients with high SAA content is also TLR2 and TLR4 dependent. Taken together, the TLR2 and TLR4 receptors are functional SAA receptors mediating MCP-1 release. Furthermore, the TLR2 and TLR4 are receptors for dysfunctional HDL. These results give a further inside in SAA as uremic toxin involved in uremia-related pro-inflammatory response in the vascular wall.
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