Combined Methylglyoxal Scavenger and Collagen Hydrogel Therapy Prevents Adverse Remodeling and Improves Cardiac Function Post-Myocardial Infarction
| Autoři | |
|---|---|
| Rok publikování | 2022 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Advanced Functional Materials |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://onlinelibrary.wiley.com/doi/epdf/10.1002/adfm.202108630 |
| Doi | http://dx.doi.org/10.1002/adfm.202108630 |
| Klíčová slova | antioxidant; fisetin; injectable hydrogel; methylglyoxal; myocardial infarction |
| Popis | 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. |