Cardioprotective effect of Notch signaling on the development of myocardial infarction complicated by diabetes mellitus
Affiliations: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China, Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning 110122, P.R. China
- Published online on: August 16, 2017 https://doi.org/10.3892/etm.2017.4932
- Pages: 3447-3454
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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The present study aimed to elucidate the role of Notch signaling in the development of myocardial infarction (MI) concomitant with diabetes in vivo and in vitro and evaluated the therapeutic effect of the Notch signaling in vitro. 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 in vivo 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 in vivo and in vitro via the inhibition of the Notch signaling pathway. Jagged1 may protect against MI in in vitro models by activating Notch signaling.