Hong Wang1, Lizhen Qiu2, Yake Ma3, Lusha Zhang2, Lu Chen4, Chunxiao Li2, Xiao Geng2, Xingyu You2, Xiumei Gao5. 1. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: wanghongsys@tjutcm.edu.cn. 2. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. 3. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. 4. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China; Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, Tianjin, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. 5. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China; Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: gaoxiumei@tjutcm.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Naoxintong capsules (NXT), a traditional Chinese Medical preparation, are widely used for treatment of cardiovascular diseases, while the mechanism is still unclear. MATERIALS AND METHODS: Myocardial infarction (MI) was induced by ligation of the left coronary artery in mice. Echocardiographic measurements were performed to do physiological assessments of left ventricle (LV) function. Histological and immunohistochemical staining was used to determine infarct size, capillary density, tissue endothelial nitric oxide synthase (eNOS) expression. Bone Marrow Transplantation (BMT) model and flow cytometric (FCM) analyses were applied to assay endothelial progenitor cells (EPCs) mobilization. Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR), Western blotting and enzyme-linked immunosorbent assay (ELISA) were performed to detect the expressions of vascular endothelial growth factor (VEGF), kinase domain region (KDR), phosphorylated-Akt (p-Akt), phosphorylated-eNOS (p-eNOS). RESULTS: NXT administration reduced myocardium fibrosis and increased myocardium capillary density in response to MI. NXT increased circulating Sca1+/ Fetal liver kinase 1 (Flk1)+ mononuclear cells (MNCs) and soluble Kit ligand (sKitL) of bone marrow (BM) in response to MI. In mice transplanted with green fluorescent protein (GFP) BM cells, NXT increased the numbers of GFP-positive cells at the border zone of the ischemic region in MI-induced mice. NXT increased the numbers of eNOS-expressing BM-derived cells in tissues, which was involved in increased the expressions of VEGF, KDR, p-eNOS, p-Akt in the myocardium. CONCLUSION: NXT-mediated recovery in MI-induced mice was involved in mobilization and incorporation of bone marrow-derived EPCs/circulating angiogenic cells (CACs) leading to enhancement of neovascularization via VEGF/eNOS signaling.
ETHNOPHARMACOLOGICAL RELEVANCE: Naoxintong capsules (NXT), a traditional Chinese Medical preparation, are widely used for treatment of cardiovascular diseases, while the mechanism is still unclear. MATERIALS AND METHODS:Myocardial infarction (MI) was induced by ligation of the left coronary artery in mice. Echocardiographic measurements were performed to do physiological assessments of left ventricle (LV) function. Histological and immunohistochemical staining was used to determine infarct size, capillary density, tissue endothelial nitric oxide synthase (eNOS) expression. Bone Marrow Transplantation (BMT) model and flow cytometric (FCM) analyses were applied to assay endothelial progenitor cells (EPCs) mobilization. Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR), Western blotting and enzyme-linked immunosorbent assay (ELISA) were performed to detect the expressions of vascular endothelial growth factor (VEGF), kinase domain region (KDR), phosphorylated-Akt (p-Akt), phosphorylated-eNOS (p-eNOS). RESULTS:NXT administration reduced myocardium fibrosis and increased myocardium capillary density in response to MI. NXT increased circulating Sca1+/ Fetal liver kinase 1 (Flk1)+ mononuclear cells (MNCs) and soluble Kit ligand (sKitL) of bone marrow (BM) in response to MI. In mice transplanted with green fluorescent protein (GFP) BM cells, NXT increased the numbers of GFP-positive cells at the border zone of the ischemic region in MI-induced mice. NXT increased the numbers of eNOS-expressing BM-derived cells in tissues, which was involved in increased the expressions of VEGF, KDR, p-eNOS, p-Akt in the myocardium. CONCLUSION:NXT-mediated recovery in MI-induced mice was involved in mobilization and incorporation of bone marrow-derived EPCs/circulating angiogenic cells (CACs) leading to enhancement of neovascularization via VEGF/eNOS signaling.