Myocardial protection by nanomaterials formulated with CHIR99021 and FGF1

Chengming Fan, Yasin Oduk, Meng Zhao, Xi Lou, Yawen Tang, Danielle Pretorius, Mani T. Valarmathi, Gregory P. Walcott, Jinfu Yang, Philippe Menasche, Prasanna Krishnamurthy, Wuqiang Zhu, Jianyi Zhang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article numbere132796
JournalJCI Insight
Volume5
Issue number12
DOIs
StatePublished - Jun 18 2020

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Myocardial protection by nanomaterials formulated with CHIR99021 and FGF1'. Together they form a unique fingerprint.

Cite this