This preprint is under consideration at Cardiovascular Drugs and Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research Article
Yongjian Wang
Nankai University College of Life Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1035-6070
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Purpose
Anti-inflammatory therapy is important for reducing myocardial injury after acute myocardial infarction (MI). New anti-inflammatory drugs and their mechanism are necessary to be explored to improve the clinical efficacy. We aimed to improve the efficacy of colchicine on attenuating MI injury by nano-drug delivery systems, and to investigate the mechanism of anti-inflammatory.
Methods
Colchicine-containing delivery system based on calcium carbonate nanoparticles (ColCaNPs) was synthesized. The protection against MI by ColCaNPs was evaluated using an in vivo rat model established by ligating the left anterior descending coronary artery. Macrophage polarization and the levels of inflammatory cytokines were determined using immunohistochemistry, western blot and ELISA analysis.
Results
ColCaNPs treatment showed about a 45% reduction in myocardial infarct size and attenuating myocardial fibrosis compared with groups without drug intervention after MI. Furthmore, ColCaNPs significantly decreased the levels of CRP, TNF-α and IL-1β in serum and the expression of proinflammatory cytokine in myocardial tissues after MI (p < 0.05). We also found that ColCaNPs notably restrained pyroptosis, and inhibited inflammatory response by modulating on M1/M2 macrophage polarization and suppressing TLR4/NFκB/NLRP3 signal pathway.
Conculsion
Colchicine-containing nanoparticles can protect against MI injury in a clinically relevant rat model by reducing inflammation. In addition, calcium carbonate nanoparticles can increase the cardioprotective effects of colchicine.
Keywords
Acute myocardial infarction, pyroptosis, macrophage polarization, inflammatory response, colchicine, nanoparticles
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CURRENT STATUS: Under Review
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Posted 25 Apr, 2021
Editor assigned
On 25 Apr, 2021
Reviewers invited
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Received 25 Apr, 2021
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This preprint is under consideration at Cardiovascular Drugs and Therapy. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Yongjian Wang
Nankai University College of Life Sciences
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1035-6070
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version (no preprint)
Posted 25 Apr, 2021
Editor assigned
On 25 Apr, 2021
Reviewers invited
Invitations sent on 25 Apr, 2021
Reviews received
Received 25 Apr, 2021
First submitted
On 16 Apr, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Purpose
Anti-inflammatory therapy is important for reducing myocardial injury after acute myocardial infarction (MI). New anti-inflammatory drugs and their mechanism are necessary to be explored to improve the clinical efficacy. We aimed to improve the efficacy of colchicine on attenuating MI injury by nano-drug delivery systems, and to investigate the mechanism of anti-inflammatory.
Methods
Colchicine-containing delivery system based on calcium carbonate nanoparticles (ColCaNPs) was synthesized. The protection against MI by ColCaNPs was evaluated using an in vivo rat model established by ligating the left anterior descending coronary artery. Macrophage polarization and the levels of inflammatory cytokines were determined using immunohistochemistry, western blot and ELISA analysis.
Results
ColCaNPs treatment showed about a 45% reduction in myocardial infarct size and attenuating myocardial fibrosis compared with groups without drug intervention after MI. Furthmore, ColCaNPs significantly decreased the levels of CRP, TNF-α and IL-1β in serum and the expression of proinflammatory cytokine in myocardial tissues after MI (p < 0.05). We also found that ColCaNPs notably restrained pyroptosis, and inhibited inflammatory response by modulating on M1/M2 macrophage polarization and suppressing TLR4/NFκB/NLRP3 signal pathway.
Conculsion
Colchicine-containing nanoparticles can protect against MI injury in a clinically relevant rat model by reducing inflammation. In addition, calcium carbonate nanoparticles can increase the cardioprotective effects of colchicine.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
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