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Phosphodiesterase-5a Knock-out Suppresses Inflammation by Down-Regulating Adhesion Molecules in Cardiac Rupture Following Myocardial Infarction

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Abstract

Cardiac rupture is a fatal complication of acute myocardial infarction (MI), associated with increased inflammation and damaged extracellular matrix. C57BL/6 J wild type (WT) and Pde5a knockout (Pde5a−/−) mice were selected to establish MI model. The rupture rate of Pde5a−/− mice was significantly reduced (P < 0.01) within 7 days post MI. The cardiac function of Pde5a−/− mice was better than WT mice both at day 3 and 7 post MI. Immunohistochemical staining and flow cytometry showed neutrophils and macrophages were decreased in Pde5a−/− mouse hearts. Inflammatory factors expression such as IL-1β, IL-6, IL-8, Mcp-1, TNF-α significantly decreased in Pde5a−/− mice post MI. Moreover, western blot showed the inhibition of inflammatory response was accompanied by down-regulation of intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) in Pde5a−/− mice. Knockout of Pde5a reduced inflammatory cells infiltration by down-regulating the expression of ICAM-1 and VCAM-1, and prevented early cardiac rupture after MI. All authors declare that they have no conflicts of interest. This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and institutional guidelines for the care and use of animals were followed.

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Funding

This study was funded by grants from the National Natural Science Foundation of China (81970292, 81600213, 81670222 and 81700262). Beijing Natural Science Foundation (7191002). Beijing Hospitals Authority Youth Program (QML20190603). Capital’s Funds for Health Improvement and Research (2018–1-2061). CS Optimizing Antithrombotic Research Fund (BJUHFCSOARF201901–08). Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201710), Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20180601).

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Authors and Affiliations

  1. Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China

    Siyi Li, Youcai Ma, Yan Yan, Xiao Wang, Wei Gong & Shaoping Nie

  2. Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China

    Siyi Li, Youcai Ma, Yan Yan, Xiao Wang, Wei Gong & Shaoping Nie

  3. Department of Cardiology, China-Japan Friendship Hospital, Beijing, China

    Mengwen Yan

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  1. Siyi Li
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  2. Youcai Ma
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  3. Yan Yan
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  4. Mengwen Yan
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  5. Xiao Wang
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  6. Wei Gong
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  7. Shaoping Nie
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Correspondence to Wei Gong or Shaoping Nie.

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Li, S., Ma, Y., Yan, Y. et al. Phosphodiesterase-5a Knock-out Suppresses Inflammation by Down-Regulating Adhesion Molecules in Cardiac Rupture Following Myocardial Infarction. J. of Cardiovasc. Trans. Res. 14, 816–823 (2021). https://doi.org/10.1007/s12265-021-10102-2

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