Recombinant Human Collagen Hydrogel Rapidly Reduces Methylglyoxal Adducts within Cardiomyocytes and Improves Borderzone Contractility after Myocardial Infarction in Mice. (24th May 2022)

• Record Type: Journal Article
• Authors: McLaughlin, Sarah; Sedlakova, Veronika; Zhang, Qingzhou; McNeill, Brian; Smyth, David; Seymour, Richard; Davis, Darryl R.; Ruel, Marc; Brand, Marjorie; Alarcon, Emilio I.; Suuronen, Erik J.
• Is Part Of: Advanced functional materials. Volume 32:Number 32(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-24
• Subjects: collagen hydrogels -- erythroid differentiation regulator 1 -- methylglyoxal -- myocardial infarction -- ventricular remodeling; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.202204076
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: Methylglyoxal (MG) production after myocardial infarction (MI) leads to advanced glycation end‐product formation, adverse remodeling, and loss of cardiac function. The extracellular matrix (ECM) is a main target for MG glycation. This suggests that ECM‐mimicking biomaterial therapies may protect the post‐MI environment by removing MG. In this study, mechanisms by which a recombinant human collagen type I hydrogel therapy confers cardioprotection are investigated. One‐week post‐MI, mice receive intramyocardial injection of hydrogel or PBS. The hydrogel improves border zone contractility after 2 days, which is maintained for 28 days. RNA sequencing shows that hydrogel treatment decreases the expression of erythroid differentiation regulator 1, a factor associated with apoptosis. Hydrogel treatment reduces cardiomyocyte apoptosis and oxidative stress at 2 days with greater myocardial salvage seen at 28 days. The hydrogel located at the epicardial surface is modified by MG, and less MG‐modified proteins are observed in the underlying myocardium of hydrogel‐treated mice. Biomaterials that can be a target for MG glycation may act as a sponge to remove MG from the myocardium post‐MI. This leads to less oxidative stress, greater survival and contractility of cardiomyocytes, which altogether suggests a novel mechanism by which biomaterials improve function of the infarcted heart. Abstract : A collagen hydrogel is used to treat myocardial infarction (MI). The hydrogel acts as a sponge to remove the toxic product methylglyoxal, which accumulates after MI. This decreases oxidative stress, reduces cell death, increases contractility, and improves cardiac function. This highlights a novel mechanism by which biomaterials improve function of the infarcted heart through the removal of methylglyoxal.