| Literature DB >> 32453715 |
Chengming Fan1,2, Yasin Oduk1, Meng Zhao1, Xi Lou1, Yawen Tang1, Danielle Pretorius1, Mani T Valarmathi1, Gregory P Walcott1, Jinfu Yang2, Philippe Menasche1,3, Prasanna Krishnamurthy1, Wuqiang Zhu1, Jianyi Zhang1.
Abstract
The mortality of patients suffering from acute myocardial infarction is linearly related to the infarct size. As regeneration of cardiomyocytes from cardiac progenitor cells is minimal in the mammalian adult heart, we have explored a new therapeutic approach, which leverages the capacity of nanomaterials to release chemicals over time to promote myocardial protection and infarct size reduction. Initial screening identified 2 chemicals, FGF1 and CHIR99021 (a Wnt1 agonist/GSK-3β antagonist), which synergistically enhance cardiomyocyte cell cycle in vitro. Poly-lactic-co-glycolic acid nanoparticles (NPs) formulated with CHIR99021 and FGF1 (CHIR + FGF1-NPs) provided an effective slow-release system for up to 4 weeks. Intramyocardial injection of CHIR + FGF1-NPs enabled myocardial protection via reducing infarct size by 20%-30% in mouse or pig models of postinfarction left ventricular (LV) remodeling. This LV structural improvement was accompanied by preservation of cardiac contractile function. Further investigation revealed that CHIR + FGF1-NPs resulted in a reduction of cardiomyocyte apoptosis and increase of angiogenesis. Thus, using a combination of chemicals and an NP-based prolonged-release system that works synergistically, this study demonstrates a potentially novel therapy for LV infarct size reduction in hearts with acute myocardial infarction.Entities:
Keywords: Cardiology; Cardiovascular disease; Cell cycle; Nanotechnology; Therapeutics
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Year: 2020 PMID： 32453715 PMCID： PMC7406256 DOI： 10.1172/jci.insight.132796
Source DB: PubMed Journal: JCI Insight ISSN： 2379-3708