Hypoxia-Inducible Factor 1 alpha (HIF-1α)/Vascular Endothelial Growth Factor (VEGF) Pathway Participates in Angiogenesis of Myocardial Infarction in Muscone-Treated Mice: Preliminary Study

Abstract

BackgroundAngiogenesis plays a crucial role in myocardial infarction (MI) treatment by ameliorating myocardial remodeling, thus improving cardiac function and preventing heart failure. Muscone has been reported to have beneficial effects on cardiac remodeling in MI mice. However, the effects of muscone on angiogenesis in MI mice and its underlying mechanisms remain unknown.Material/MethodsMice were randomly divided into sham, MI, and MI+muscone groups. The MI mouse model was established by ligating the left anterior descending coronary artery. Mice in the sham group received the same procedure except for ligation. Mice were administered muscone or an equivalent volume of saline for 4 consecutive weeks. Cardiac function was evaluated by echocardiograph after MI for 2 and 4 weeks. Four weeks later, all mice were sacrificed and Masson’s trichrome staining was used to assess myocardial fibrosis. Isolectin B4 staining was applied to evaluate the angiogenesis in mouse hearts. Immunohistochemistry, Western blot analysis, and quantitative real-time polymerase chain reaction (qPCR) were performed to analyze expression levels of HIF-1α and its downstream genes.ResultsCompared with the MI group, muscone treatment significantly improved cardiac function and reduced myocardial fibrosis. Moreover, muscone enhanced angiogenesis in the peri-infarct region and p-VEGFR2 expression in the vascular endothelial cells. Western blot analysis and qPCR showed that muscone upregulated expression levels of HIF-1α and VEGFA.ConclusionsMuscone improved cardiac function in MI mice through augmented angiogenesis. The potential mechanism of muscone treatment in regulating angiogenesis of MI mice was upregulating expression levels of HIF-1α and VEGFA.

Herbal complex 'Buyang Huanwu Tang' improves motor endplate function of denervated-dependent skeletal muscle atrophy in rat

“…The skeletal muscle growth is correlated with the VEGF expression due to the previously published report (Du et al, 2018). Our results illustrated that BYHWT treatment remarkably enhanced VEGF levels that reduced in the Model group ( Fig.…”

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

“…Moreover, overlapping targets of Huangqi and HF had similar biological processes and multitarget synergistic characteristics. For example, enhancing autophagy of cardiomyocytes by inhibiting AKT1 expression and VEGFA increase contribute to improved cardiac dysfunction, angiogenesis, and remodeling [40,41]. Elevation of IL-6 and IL-1β can induce cardiomyocyte apoptosis and reduce ventricular wall compliance and cause coronary microvascular endothelial inflammation [42].…”

Muscone Ameliorates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κb Ligand-Induced Osteoclastogenesis by Suppressing TNF Receptor–Associated Factor 6-Mediated Signaling Pathways

“…It is used in a large number of fine perfumes (Callejo et al, 2016). And it is also known as an effective drug with anti-inflammatory effects for multiple systems (Wang et al, 2014;Liu et al, 2014;Du et al, 2018). Since postmenopausal osteoporosis is regarded to be deteriorated by the inflammatory status due to the withdrawal of estrogen, and osteoclasts are then induced by pro-inflammatory cytokines, we hypothesized that muscone might also have effects on osteoclastogenesis and bone loss.…”

“…Muscone (MUS), 3-methylcyclopentadecanone, is the main ingredient of musk ( Figure 1A). It is used to treat myocardial infarction (Wang et al, 2014;Du et al, 2018), relieve pain, and promote fractures . Furthermore, it has been proved to have anti-inflammatory effects on multiple systems (Wang et al, 2014;Liu et al, 2014).…”