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• W2890167942 abstract "Myocardial infarction (MI) contributes to the development of cardiac remodeling and heart failure. Insufficient post-MI myocardial angiogenesis has been identified as a non-negligible event which precipitates heart failure progression. Previous studies reported that cytochrome P450 epoxygenase and its metabolites exerted beneficial effects on cardiovascular diseases. However, the role of cytochrome P450 2J2 (CYP2J2) in post-MI heart failure is incompletely understood.First, western blot and real-time PCR analyses showed that CYP2J2 expression increased clearly in patients with acute MI and old MI, compared to control. Second, echocardiography and histological studies showed that transgenic (TG) rats had relatively preserved cardiac function, as well as attenuated remodeling, and reduced scar formation, compared to the wild-type (WT) littermates after MI eight weeks. Importantly, the cardioprotective effect induced by CYP2J2 overexpression was abrogated by VEGFR2 inhibitor-cediranib. More intriguingly, positron emission computed Tomography (PET) analyses showed that TG rats displayed better myocardial perfusion than WT rats. We found that these effects were linked to increasing circulating EETs and enhancing myocardial angiogenesis. Additionally, in vitro study demonstrated that 11, 12-epoxyeicosatrienoic acid (11, 12-EET) induced more robust tube formation and markedly increased VEGF-A and bFGF expression in hypoxia and normoxia. Finally, western blot analyses uncovered that CYP2J2 and 11, 12-EET promoted angiogenesis via the Jagged1/Notch1 signaling pathway.Our findings demonstrate that CYP2J2 improves cardiac function by increasing the concentration of circulating EETs, and boosting angiogenesis via the Jagged1/Notch1 signaling pathway in MI-induced heart failure." @default.
• W2890167942 created "2018-09-27" @default.
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• W2890167942 date "2018-10-01" @default.
• W2890167942 modified "2023-09-24" @default.
• W2890167942 title "Endothelium-specific CYP2J2 overexpression improves cardiac dysfunction by promoting angiogenesis via Jagged1/Notch1 signaling" @default.
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• W2890167942 doi "https://doi.org/10.1016/j.yjmcc.2018.08.027" @default.
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