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American Heart Association

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Final ID: Su2121

IL-37 promotes resolution of Right Heart Disease-induced inflammation and atrial fibrillation.

Abstract Body (Do not enter title and authors here): INTRODUCTION: Atrial Fibrillation (AF) is the most common cardiac arrhythmia. Hypertension, obesity, diabetes or right heart disease (RHD) are important risk factors for AF. Inflammation stands as a common denominator among most AF risk factors. Studies have shown that patients with AF present high levels of circulating IL-18. Our group recently described that inflammation-resolution may prevent AF in RHD, however, the mechanism remains unclear. To inhibit IL-18-induced inflammation, IL37, a specific antagonist of IL-18-receptor was shown to attenuate cardiac fibrosis in a mice model of myocardial infarction, but little is known about its efficacy to prevent AF.

HYPOTHESIS: IL-37 curbs RHD-induced atrial inflammation and AF vulnerability.

METHODS: To induce right-sided cardiac hypertrophy and dilation, pulmonary artery banding (PAB) was performed in male and female Wistar rats (250-300g). Sham animals did not receive the ligation. Animals were randomized into four groups: Sham and PAB treated or not with IL37 (100 ng/ml/kg). Electrophysiological studies and echocardiography were performed in vivo before sacrifices at day (D)0, D7, D14 and D21. To analyze the atrial conduction, right atrial (RA) optical mapping was performed on Langendorff-perfused hearts. Histology, western blot, and qPCR were performed to study the expression of proteins and genes involved in atrial inflammation, fibrosis, and electrical remodeling.

RESULTS: Twenty-one days after surgery, PAB rats were more vulnerable to AF and developed severe right-sided hypertrophy and dilation compared to Sham. Reliable to clinical evidence, female rats might be more resistant to AF than males. AF was associated with increased RA levels of inflammatory biomarkers including IL18, IL1β, and IL6. IL37 treatment was associated with decreased atrial expression of inflammatory markers.

CONCLUSION: IL37 is a potential new therapeutic strategy to reduce atrial inflammation and prevent AF vulnerability in RHD.
  • Neuilly, Orlane  ( Montreal Hearth Institut, Université de Montreal , Montreal , Quebec , Canada )
  • Tanguay, Jean-francois  ( Montreal Heart Institut , Montreal , Quebec , Canada )
  • Tardif, Jean-claude  ( Montreal Heart Institut , Montreal , Quebec , Canada )
  • Hiram, Roddy  ( Montreal Hearth Institut, Université de Montreal , Montreal , Quebec , Canada )
  • Younes, Rim  ( Montreal Heart Institut , Montreal , Quebec , Canada )
  • Mehdizadeh, Mozhdeh  ( Montreal Heart Institut , Montreal , Quebec , Canada )
  • Leblanc, Charles-alexandre  ( Montreal Heart Institut , Montreal , Quebec , Canada )
  • Xiong, Feng  ( Montreal Heart Institut , Montreal , Quebec , Canada )
  • Naud, Patrice  ( Montreal Heart Institut , Montreal , Quebec , Canada )
  • Xiao, Jiening  ( Montreal Heart Institut , Montreal , Quebec , Canada )
  • Roy, Colombe  ( Montreal Heart Institut , Montreal , Quebec , Canada )
  • Sirois, Martin  ( Montreal Heart Institute , Montreal , Quebec , Canada )
  • Author Disclosures:
    Orlane Neuilly: DO NOT have relevant financial relationships | Jean-Francois Tanguay: No Answer | Jean-Claude Tardif: DO have relevant financial relationships ; Research Funding (PI or named investigator):Amarin:Past (completed) ; Research Funding (PI or named investigator):Boeringher-Ingelheim:Active (exists now) ; Research Funding (PI or named investigator):Novo-Nordisk:Active (exists now) ; Consultant:DalCor Pharmaceuticals:Active (exists now) ; Ownership Interest:DalCor Pharmaceuticals:Active (exists now) ; Speaker:Pfizer:Active (exists now) ; Speaker:Pendopharm:Past (completed) ; Speaker:HLS Pharmaceuticals:Past (completed) ; Research Funding (PI or named investigator):Pfizer:Active (exists now) ; Research Funding (PI or named investigator):Novartis:Active (exists now) ; Research Funding (PI or named investigator):Merck:Active (exists now) ; Research Funding (PI or named investigator):Esperion:Active (exists now) ; Research Funding (PI or named investigator):DalCor Pharmaceuticals:Active (exists now) ; Research Funding (PI or named investigator):Ceapro:Active (exists now) ; Research Funding (PI or named investigator):AstraZeneca:Past (completed) | Roddy Hiram: DO NOT have relevant financial relationships | Rim Younes: No Answer | Mozhdeh Mehdizadeh: DO have relevant financial relationships ; Employee:Milestone pharmaceuticals:Active (exists now) | Charles-Alexandre LeBlanc: No Answer | Feng Xiong: No Answer | Patrice Naud: No Answer | Jiening Xiao: DO NOT have relevant financial relationships | Colombe Roy: DO NOT have relevant financial relationships | Martin Sirois: No Answer
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Novel Mechanistic Insights Into Arrhythmogenesis: There Is More Than Meets the Eye!

Sunday, 11/17/2024 , 03:15PM - 04:15PM

Abstract Poster Session

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