Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial ischemia-reperfusion (MI/R) injury is characterized by iron deposition and reactive oxygen species production, which can induce ferroptosis. Ferroptosis has also been proposed to promote cardiomyocyte death. The current study sought to define the mechanism governing cardiomyocyte death in MI/R injury. An animal model of MI/R was established by ligation and perfusion of the left anterior descending coronary artery, and a cellular model of IR was constructed in cardiomyocytes. ChIP assay was then conducted to determine the interaction among USP22, SIRT1, p53, and SLC7A11. Loss- and gain-of-function assays were also conducted to determine the in vivo and in vitro roles of USP22, SIRT1, and SLC7A11. The infarct size and pathological changes of myocardial tissue were observed using TCC and hematoxylin-eosin staining, and the levels of cardiac function- and myocardial injury-related factors of rats were determined. Cardiomyocyte viability and apoptosis were evaluated in vitro, followed by detection of ferroptosis-related indicators (glutathione (GSH), reactive oxygen species, lipid peroxidation, and iron accumulation). USP22, SIRT1, and SLC7A11 expressions were found to be down-regulated, whereas p53 was highly expressed during MI/R injury. USP22, SIRT1, or SLC7A11 overexpression reduced the infarct size and ameliorated pathological conditions, cardiac function, as evidenced by reduced maximum pressure, ejection fraction, maximum pressure rate, and myocardial injury characterized by lower creatine phosphokinase and lactate dehydrogenase levels in vivo. Moreover, USP22, SIRT1, or SLC7A11 elevation contributed to enhanced cardiomyocyte viability and attenuated ferroptosis-induced cell death in vitro, accompanied by increased GSH levels, as well as decreased reactive oxygen species production, lipid peroxidation, and iron accumulation. Together, these results demonstrate that USP22 overexpression could inhibit ferroptosis-induced cardiomyocyte death to protect against MI/R injury via the SIRT1/p53/SLC7A11 association.
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PMID:USP22 Protects Against Myocardial Ischemia-Reperfusion Injury via the SIRT1-p53/SLC7A11-Dependent Inhibition of Ferroptosis-Induced Cardiomyocyte Death. 3319 49

Caloric restriction (CR) is a novel dietary therapy that has a protective effect on myocardial ischemia. However, the mechanisms underlying the therapeutic effect of CR remain unclear. Transfer RNA-derived small RNAs (tsRNAs) are a novel type of short non-coding RNAs that have potential regulatory functions in various physiological and pathological processes. In this study, we explored new therapeutic targets of CR through tsRNA sequencing. Rats were randomly divided into three groups: a normal control group (norm group), isoproterenol (ISO)-induced myocardial ischemic group (MI group), and CR pretreatment plus ISO-induced myocardial ischemic group (CR + MI group). Triphenyl tetrazolium chloride staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, serum creatine kinase (CK) and lactic acid dehydrogenase activity detection kits, and creatine kinase isoenzyme 1 levels were used to measure the degree of myocardial ischemic injury. These indicators of myocardial ischemia were significantly improved in the CR + MI group compared with those in the MI group. In the ischemic myocardial tissue of the MI group, a total of 708 precisely matched tsRNAs were identified, and 302 tsRNAs (fold change >1.5, P < 0.05) were significantly changed when compared with those in the norm group. Furthermore, 55 tsRNAs were significantly regulated by CR pretreatment, among which five tsRNAs (tiRNA-His-GTG-004, tRF-Gly-TCC-018, tRF-Cys-GCA-022, tRF-Lys-CTT-026, tRF-Met-CAT-008) were randomly selected and verified by quantitative real-time polymerase chain reaction. In addition, predictions of target genes and bioinformatics analysis indicated that these tsRNAs may play a therapeutic role through the regulation of macromolecular metabolism. In conclusion, our findings reveal that tsRNAs are potential therapeutic targets for CR pre-pretreatment to improve myocardial ischemic injury. This study provides new ideas for future research on elucidating the mechanisms of CR pretreatment in ameliorating myocardial ischemic injury.
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PMID:Systematic Analysis of tRNA-Derived Small RNAs Discloses New Therapeutic Targets of Caloric Restriction in Myocardial Ischemic Rats. 3322 44