Cardioprotective effect of Notch signaling on the development of myocardial infarction complicated by diabetes mellitus.

The present study aimed to elucidate the role of Notch signaling in the development of myocardial infarction (MI) concomitant with diabetes and and evaluated the therapeutic effect of the Notch signaling . Streptozotocin-induced diabetic rats were subjected to 25 min of ischemia and 2 h of reperfusion. Cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) isoenzyme levels were detected. Infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining. Myocardial apoptosis and fibrosis were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Masson Trichrome staining, respectively. The mRNA and protein levels of Notch signaling components, including Notch1, Notch4, Delta-like 1, Jagged1, Mastermind-like protein 1 and p300, were quantified by reverse transcription-quantitative polymerase chain reaction and western blotting analyses, respectively. H9c2 cells were treated with/without 33 mM high glucose (HG) and/or subjected to hypoxia in the presence/absence of Jagged1. Cell viability and apoptosis were determined by MTT assay and Annexin V-fluorescein isothiocyanate/propidium iodide assay. Levels of the Notch signaling pathway members were examined. The present findings revealed that diabetes elevated CK-MB and cTnT, increased infarct size, induced myocardial apoptosis and inhibited the Notch signaling pathway after ischemia/reperfusion. Ischemia/reperfusion augmented the severity of MI in diabetic rats. Furthermore, HG reduced cell viability and induced cell apoptosis in H9c2 cells after hypoxia exposure, which was inhibited by Jagged1. We also found that HG inhibited Notch signaling in H9c2 cells after hypoxia, whereas Jagged1 exerted its cardioprotective effect on hypoxic injury (in HG environments or not) by activating the Notch signaling pathway. In conclusion, these findings suggest that diabetes promoted the progression of MI and via the inhibition of the Notch signaling pathway. Jagged1 may protect against MI in models by activating Notch signaling.