ArticleJournal of advanced research2024
Evolocumab prevents atrial fibrillation in rheumatoid arthritis rats through restraint of PCSK9 induced atrial remodeling.
Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Genomic data-driven framework for drug target discovery in atrial fibrillation.Journal of translational medicine · 2025Pooled it
- Low-intensity pulsed ultrasound promotes peripheral nerve regeneration by alleviating Schwann cells pyroptosis.Communications biology · 2026Article
- Molecular Mechanisms of Atrial Fibrillation Recurrence After Successful Catheter Ablation.Cells · 2025Review
- Targeted nanodelivery strategies for atrial fibrillation: concomitant targeting of fibrosis suppression and electrical conduction restoration through advanced nanobiotechnology.Journal of nanobiotechnology · 2025Review
- Association between proprotein convertase subtilisin/kexin type 9 targeted therapies and the risk of arrhythmias: a meta-analysis of randomized controlled trials.American journal of preventive cardiology · 2025Article
- Proteome-wide Mendelian randomization identifies drug targets for atrial fibrillation/flutter.BMC cardiovascular disorders · 2025Article
- Evolocumab attenuates myocardial ischemia/reperfusion injury by blocking PCSK9/LIAS-mediated cuproptosis of cardiomyocytes.Basic research in cardiology · 2025Article
- Serum Lipids, Inflammation, and the Risk of Atrial Fibrillation: Pathophysiological Links and Clinical Evidence.Journal of clinical medicine · 2025Review
- Beyond joints: the importance of animal models in exploring rheumatoid arthritis comorbidities.Frontiers in medicine · 2025Review
- Exploring the Pleiotropy of PCSK9: A Wide Range of Influences from Lipid Regulation to Extrahepatic Function.Journal of inflammation research · 2025Review
- Drug Target Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Atrial Fibrillation.Cardiology · 2024Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionProprotein convertase subtilisin/kexin type 9 (PCSK9) is implicated in the pathogenesis and progression of autoimmune disease. Patients with rheumatoid arthritis (RA) are at high risk of developing atrial fibrillation (AF), while whether PCSK9 is involved in the onset of AF among RA patients remains unclear.
objectivesTo explore the role of PCSK9 in the occurrence of AF in RA patients and decipher the underlying mechanism.
methodsWe established a rat model of collagen-induced arthritis (CIA) by immunization with type II collagen in Freund's incomplete adjuvant. Atrial electrophysiological test was used to evaluate AF susceptibility. We performed a clinical study to examine the correlation between PCSK9 level and AF, which recruited healthy control, RA patients and RA patients complicated with AF. Evolocumab (a monoclonal antibody of PCSK9) is administered via intraperitoneal injection in CIA rats to assess the role of PCSK9 in RA-related AF. LPS-RS (LPS inhibitor), clodronate liposomes (depletion of macrophages), and cell co-culture model were used to dissect the mechanism underlying PCSK9 promotes AF.
resultsAF inducibility and duration were higher in CIA rats, accompanied by elevated plasma and atrial PCSK9. Interestingly, compared with healthy control subjects, patients with RA showed an increase in PCSK9, and the PCSK9 is much higher in RA patients complicated with AF. The level of PCSK9 was independently associated with AF risk in RA patients. In the in vivo experiment, evolocumab reduced AF susceptibility, and ameliorated atrial structural remodeling of CIA rats. Mechanistically, augmented LPS in CIA rats led to an increase in PCSK9, which exacerbated fibrosis of cardiac fibroblasts and apoptosis of cardiac myocytes by enhancement of M1 macrophages polarization and inflammation, thereby contributing to AF.
conclusionThis study suggests that elevated PCSK9 causes atrial structural remodeling by enhancement of M1 macrophages polarization in atria, and evolocumab can effectively protects CIA rats from AF.
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