Combined Methylglyoxal Scavenger and Collagen Hydrogel Therapy Prevents Adverse Remodeling and Improves Cardiac Function Post-Myocardial InfarctionShow others and affiliations
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
2021-10-252021-10-252022-03-14