Western blots of Akt, its phosphorylated isoform P-Akt, eNOS, its phosphorylated isoform P-eNOS, HIF-1 and Nrf2 in all 1-Methoxyphenazine methosulfate accessible samples (meanEM, n=6/six and five/five with no and with wortmannin, respectively). , P<0.05 with respect to control, Student's two-tailed t-test embryonic vasculature, binds to either one of the VEGF-R isoforms, but the VEGF-R2/flk-1 isoform is known to mediate the majority of cell responses to VEGF-A . VEGF-A binding causes VEGF-R2 dimerization and activation through a Figure 6. Cardioprotection. Panel A. Representative images taken in a control and a IH heart after staining myocardial tissues slices with triphenyltetrazolium chloride to mark the infarct and risk areas. Whereas the blue and white areas represent viable and necrotic tissues, respectively, the red+white area represents the area at risk. Panel B. Box-and-whisker plots from all the hearts subjected to LAD occlusion and reperfusion. The boxes represent the 2nd and 3rd quartiles of data, with the whisker delimiting the min-max range. The "+" represents the mean (n=10/7 and 5/5 without and with wortmannin, respectively). The insets report the ANOVA values. Panel C. Left: Representative Oxyblot (Oxy) analysis. Right: Loading of the same nitrocellulose sheet as visualized by Red Ponceau (RP) staining. Panel D. Normalized densitometry values (Oxy/RP), index of protein carbonylation. , P<0.05 with respect to control , P<0.05 with respect to PRE-LAD (ANOVA one-way test, followed by the Bonferroni multiple comparison procedure, two tailed, the inset reports the value of the ANOVA P, n=6/6 and 8/5, pre-LAD and postLAD, respectively)pathway leading to PLC- activation, increase in cytoplasm Ca+ + , activation of protein kinase C and phosphorylation of at least two of the mitogen-activated protein kinases, e.g., extracellular signal-regulated kinases ERK1/2 and p38 , which then move to the nucleus where they participate to various transcriptional activities leading to cell proliferation and migration . Of interest, an OSA-like IH paradigm increases VEGF immunoreactivity in the carotid body thereby enhancing carotid body chemosensory response to hypoxia . VEGF and VEGF-R2 are known downstream effectors of the hypoxia-inducible factor (HIF)-1, the master regulator of O2 homeostasis. Although it is likely that the over-expression of pro-angiogenesis factors depend on the myocardium response to hypoxia, we were unable to document significant changes in HIF-1 protein expression, perhaps due to the short hypoxia times followed by reoxygenation, which blunts HIF-1 protein over-expression . 22957729We can’t exclude, however, the occurrence of fast peaks in HIF-1 protein levels in the correspondence of the hypoxia bouts.