Expression of hypoxia-inducible factor 1 alpha ameliorate myocardial ischemia in rat

Peng, Jianqiang; Zhang, Ping; Fan, Xiaoning; Yuan, Zheng; Ming, Zhou; Guo, Ying

doi:10.1016/j.bbrc.2015.08.046

Cited by 28 publications

(13 citation statements)

References 23 publications

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“…HIF-1α is an important transcription factor that regulates the cellular response to hypoxia, and the increased expression of HIF-1α is one of the first adaptations of human myocardium to ischemia [26,27]. Previous studies using a transgenic model have found that over-expression of HIF-1α can promote angiogenesis, reduce infarct size, and improve cardiac function [28–30]. VEGFA, usually referred to as VEGF, acts as a key contributor in angiogenesis [31].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

Med Sci Monit

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2018

Med Sci Monit

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“…During hypoxia (24 h, 2% O2), apelin gene expression and secretion are increased through the activation of hypoxia inducible factor (HIF) [10, 32, 33]. Hypoxia requires a functional mitochondrial electron transport chain for the inhibition of prolyl hydroxylases and HIF stabilization [34].…”

Section: Discussionmentioning

confidence: 99%

Influence of apelin-12 on troponin levels and the rate of MACE in STEMI patients

Krasniqi

Berisha

Gashi

et al. 2017

BMC Cardiovasc Disord

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BackgroundDuring acute myocardial infarction, phosphorylated TnI levels, Ca2+ sensitivity and ATPase activity are decreased in the myocardium, and the subsequent elevation in Ca2+ levels activates protease I (caplain I), leading to the proteolytic degradation of troponins. Concurrently, the levels of apelin and APJ expression are increased by limiting myocardial injury.MethodsIn this prospective observational study, 100 consecutive patients with ST-elevation acute myocardial infarction were included. Patients meeting the following criteria were included in our study: (1) continuous chest pain lasting for >30 min, (2) observation of ST-segment elevation of more than 2 mm in two adjacent leads by electrocardiography (ECG), (3) increased cardiac troponin I levels, and (4) patients who underwent reperfusion therapy. We evaluated the levels of apelin-12 and troponin I on the first and seventh days after reperfusion therapy in all patients.ResultsApelin-12 was inversely correlated with troponin I levels (Spearman’s correlation = −0.40) with a p value <0.001. There was variability in the apelin values on the seventh day (Kruskal-Wallis test) based on major adverse cardiac events (MACE) (p = 0.012). Using ROC curve analyses, a cut-off value of >2.2 for the association of apelin with MACE was determined, and the AUC was 0.71 (95% CI, 0.58–0.84). Survival analysis using the Kaplan-Meier method showed a lower rate of MACE among patients with apelin levels >2.2 (p = 0.002), and the ROC curve analysis showed a statistically significant difference in the area under the curve (p = 0.004).ConclusionThe influence of apelin levels on troponin levels in the acute phase of STEMI is inversely correlated, whereas in the non-acute phase, low apelin values were associated with a high rate of MACE.

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“…Hypoxia-inducible factor-1α (HiF-1α), a transcription factor that is a central component of the oxygen sensing mechanism in mammalian cells, has been shown to be an important regulator in the response to hypoxia and ischemia (22,23). Previous studies have revealed that enhancing the expression of HiF-1α reduces infarct size, promotes angiogenesis and improves cardiac function (24,25). Pi3K/aKT and HiF-1α also play a substantial role in mediating the inflammatory response and oxidative stress (26,27).…”

Section: Introductionmentioning

confidence: 99%

Troxerutin attenuates oxygen‑glucose deprivation and reoxygenation‑induced oxidative stress and inflammation by enhancing the PI3K/AKT/HIF‑1α signaling pathway in H9C2 cardiomyocytes

et al. 2020

Mol Med Rep

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Myocardial ischemia-reperfusion (Mi/r) injury is a complex pathological process that occurs when tissues are reperfused following a prolonged period of ischemia. Troxerutin has been reported to have cardioprotective functions. However, the underlying mechanism by which troxerutin protects against Mi/r injury has not been fully elucidated. The aim of the present study was to explore whether troxerutin-mediated protection against oxygen-glucose deprivation/reoxygenation (oGd/r)-induced H9c2 cell injury was associated with the inhibition of oxidative stress and the inflammatory response by regulating the Pi3K/aKT/hypoxia-inducible factor-1α (HiF-1α) signaling pathway. The results of the present study suggested that troxerutin pretreatment prevented the oGd/r-induced reduction in cell viability, and the increase in lactate dehydrogenase activity and apoptosis. Troxerutin reversed oGd/r-induced the inhibition of the Pi3K/aKT/HiF-1α signaling pathway as demonstrated by the increased expression of Pi3K and HiF-1α, and the increased ratio of phosphorylated aKT/aKT. lY294002, a selective Pi3K inhibitor, inhibited the Pi3K/aKT/HiF-1α signaling pathway and further attenuated the protective effect of troxerutin against oGd/r-induced H9c2 cell damage. Furthermore, small interfering (si)rna-mediated knockdown of HiF-1α reduced troxerutin-induced protection against oGd/r injury. Troxerutin pretreatment alleviated oGd/r-induced oxidative stress, as demonstrated by the reduced generation of reactive oxygen species and malonaldehyde content, and the increased activities of superoxide dismutase and glutathione peroxidase, which were reduced by HiF-1α-sirna. Troxerutin-induced decreases in the levels of interleukin (il)-1β, il-6 and tumor necrosis factor-α in oGd/r conditions were also reduced by HiF-1α-sirna. The results from the present study indicated that troxerutin aggravated oGd/r-induced H9c2 cell injury by inhibiting oxidative stress and the inflammatory response. The primary underlying protective mechanism of troxerutin was mediated by the activation of the Pi3K/aKT/HiF-1α signaling pathway.

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Expression of hypoxia-inducible factor 1 alpha ameliorate myocardial ischemia in rat

Cited by 28 publications

References 23 publications

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

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

Influence of apelin-12 on troponin levels and the rate of MACE in STEMI patients

Troxerutin attenuates oxygen‑glucose deprivation and reoxygenation‑induced oxidative stress and inflammation by enhancing the PI3K/AKT/HIF‑1α signaling pathway in H9C2 cardiomyocytes

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