Abstract 17122: Cardioprotection With Proangiogenic Nanomaterials Formulated With CHIR99021 and FGF1

Abstract

Introduction: We aimed at to investigate whether activation of both FGF1 and Wnt1 synergistically enhances angiogenesis and render the cardioprotection in hearts with post infarction LV remodeling. Materials and methods: CHIR99021 (a Wnt1 activator) and FGF1 were encapsulated into poly lactic-co-glycolic acid nanoparticles (CHIR99021/FGF1-NPs). Ischemic heart models were generated in C57BL/6 mice or Yorkshire swine by ligation of the left anterior descending coronary. The mice were randomly divided into 6 groups: Myocardial infarction (MI) Only (n=11), MI with nanoparticles (CHIR99021 or/and FGF1 loaded) injection (n=12, each), MI with non-loaded nanoparticles injection (n=11) and Sham group (n=10). The swine were divided into 3 groups: ischemic reperfusion injury (IRI) (n=4), IRI with CHIR99021/FGF-NPs injection (n=4) and Sham group (n=4). Left ventricle function 4 week after surgery were evaluated by Echocardiography. Cell proliferation was assessed via immunostaining in ischemic hearts and in cultivated human umbilical vein endothelial cells (HUVECs) and Human vascular smooth muscle cells (HVSMCs) using the following markers: Ki67, Brdu, PH3, and Aurora B. Apoptosis was determined with TUNEL staining. Cardiac fibrosis was evaluated via Sirius red and Fast green staining (mice) and magnetic resonance imaging (swine). Results: CHIR99021/FGF1-NPs treatment attenuated fibrosis and preserved heart contractile function in mice and swine models of postinfarction LV remodeling. The proportion of cells that expressed cell cycle markers (Ki67; BrdU; Aurora B and PH3) was significantly greater in CHIR99021+FGF1 treatment group than CHIR99021, FGF1 and PBS treatment group. The proportion of apoptotic cells was significantly smaller in CHIR99021+FGF1 treatment group than in groups of control, VEGF, CHIR99021, or FGF1 treatment alone. Conclusions: CHIR99021 and FGF synergistically activate cell cycle and reduce apoptosis, which accompanied by a significant improvement of cardiac function.