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Combined Methylglyoxal Scavenger and Collagen Hydrogel Therapy Prevents Adverse Remodeling and Improves Cardiac Function Post-Myocardial Infarction
Univ Ottawa Heart Inst, Canada; Univ Ottawa, Canada.
Univ Ottawa Heart Inst, Canada; Univ Ottawa, Canada.
Univ Ottawa Heart Inst, Canada.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Univ Ottawa Heart Inst, Canada; Univ Ottawa, Canada.
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2022 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 32, no 1, article id 2108630Article in journal (Refereed) Published
Abstract [en]

Methylglyoxal (MG) is a highly reactive dicarbonyl and the main precursor of advanced glycation end-products (AGEs). After myocardial infarction (MI), MG-derived AGEs accumulate in the heart and contribute to adverse remodeling and loss of cardiac function. In this study, the flavonoid fisetin, a dicarbonyl scavenger, is used to reduce the negative effects of MG in the post-MI heart. A fisetin-loaded collagen type I hydrogel (fisetin-HG) is injected intramyocardially in mice at 3 h post-MI, and compared to fisetin-alone, hydrogel-alone, or saline treatment. Fisetin-HG treatment increases the level of glyoxalase-1 (the main MG-metabolizing enzyme), reduces MG-AGE accumulation, and decreases oxidative stress in the MI heart, which is associated with smaller scar size and improved cardiac function. Treatment with fisetin-HG also promotes neovascularization and increases the number of pro-healing macrophages in the infarct area, while reducing the number of pro-inflammatory macrophages. Taken together, the results demonstrate that the fisetin-collagen hydrogel therapy can reduce the accumulation and negative effects of MG post-MI. This therapy may be a promising approach to limit adverse cardiac remodeling, prevent damage, and preserve function of the infarcted heart.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH , 2022. Vol. 32, no 1, article id 2108630
Keywords [en]
antioxidant; fisetin; injectable hydrogel; methylglyoxal; myocardial infarction
National Category
Biomaterials Science
Identifiers
URN: urn:nbn:se:liu:diva-180494DOI: 10.1002/adfm.202108630ISI: 000706361800001OAI: oai:DiVA.org:liu-180494DiVA, id: diva2:1605583
Note

Funding Agencies|Collaborative Health Research Program grant from the Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR) [CPG-158280]; Natural Sciences and Engineering Research CouncilNatural Sciences and Engineering Research Council of Canada (NSERC) [CHRP 523794-18]; Queen Elizabeth II Graduate Scholarships in Science and Technology; Lawrence Soloway Endowed Fellowship from the University of Ottawa Heart Institute Foundation; University of Ottawa Heart Institute; Strategic Research Endowed Fund

Available from: 2021-10-25 Created: 2021-10-25 Last updated: 2022-03-14

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