Antiarrhythmic Effect of Uridine and Uridine-5’-Monophosphate in Acute Myocardial Ischemia

Bul'on, V. V.; Крылова, И. Б.; Selina, Elena N.; Rodionova, Olga M.; Евдокимова, Н. Р.; Sapronov, N. S.; Mironova, Galina D.

doi:10.1007/s10517-014-2653-3

Cited by 9 publications

(6 citation statements)

References 9 publications

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“…Some studies found that uridine had protective effects on cardiovascular diseases. Early studies by Krylova et al found that uridine and uridine-5′-monophosphate could reduce lactic acid, improve energy metabolism, and playe a protective role in myocardial ischemia and arrhythmias (including ventricular premature, ventricular tachycardia and ventricular fibrillation) ( 39 , 40 ). Recent studies found that uridine could prevent myocardial injury in ischemia and reperfusion rat models by activating mitochondrial pathway, prevented the decrease of cell energy supply and antioxidant system activity, thus improving energy supply ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

The causal effects of genetically determined human blood metabolites on the risk of atrial fibrillation

Cheng¹,

Wang²,

Hu³

2023

Front. Cardiovasc. Med.

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BackgroundBlood metabolites have been found related to atrial fibrillation (AF), but the causal role is still unclear. Mendel randomization (MR) can give information about the causality between blood metabolites and AF.MethodsTwo-sample MR analysis was used to evaluate the causality between 486 blood metabolites and AF. Firstly, the genome-wide association study (GWAS) data for AF (from Nielsen et al.) was analyzed and some metabolites were identified. Then another GWAS data for AF (from Roselli et al.) was repeatedly analyzed to verify the results. Inverse variance weighted method was mainly used to determine the causality, and MR-egger, Weighted Median, and MR-PRESSO models were used as supplements of MR. Cochran's Q test was used to assess heterogeneity. And MR-Egger intercept and MR-PRESSO global test were performed to measure pleiotropy.ResultsThe study used Bonferroni's corrected P value (P < 1.03 × 10−4) as the significance threshold. After MR analysis and replication analysis, we found two overlapped metabolites. Among which tryptophan betaine was the most significant causal metabolite in both AF GWAS data (from Nielsen et al.) (odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.76–0.90, P = 9.37 × 10−6) and AF GWAS data (from Roselli et al.) (OR = 0.82, 95% CI = 0.76–0.88, P = 2.00 × 10−7), while uridine was nominally significant metabolites in both AF GWAS data (from Nielsen et al.) (OR = 0.58, 95% CI = 0.40–0.84, P = 0.004) and AF GWAS data (from Roselli et al.) (OR = 0.56, 95% CI = 0.35–0.88, P = 0.01). And the results of sensitivity analysis showed that none of them had obvious heterogeneity or pleiotropy.ConclusionThe study identified several blood metabolites that were causally related to AF, which may provide new perspectives on the pathogenesis of AF.

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Section: Discussionmentioning

confidence: 99%

The causal effects of genetically determined human blood metabolites on the risk of atrial fibrillation

Cheng¹,

Wang²,

Hu³

2023

Front. Cardiovasc. Med.

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“…Uridine, a pyrimidine nucleoside, is more abundant in human plasma than other nucleosides 35 and is critical in the synthesis of endogenous pyrimidine, glycogen, biomembranes and the like 36 . Uridine modulates heart rhythm disorders through its participation in myocardial glycogen resynthesis and ATP production for ion transport systems under pathological conditions 37 . Fibrosis has been well established and exerts a crucial effect in the development of AF 38 .…”

Section: Discussionmentioning

confidence: 99%

Protective effect of uridine on atrial fibrillation: a Mendelian randomisation study

Xu,

Zhang,

Cheng

et al. 2023

Sci Rep

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Uridine, a pyrimidine nucleoside, is crucial in the synthesis of metabolites. According to observational studies, a higher plasma uridine level is associated with a lower risk of atrial fibrillation (AF). However, the casual relationship between uridine and AF is still unknown. In this study, we used the Mendelian randomisation (MR) approach to explore causality. Three genetic variants associated with uridine were identified from the Metabolomics GWAS server (7824 participants); summary-level datasets associated with AF were acquired from a genome-wide association study (GWAS) meta-analysis with 1,030,836 European participants (60,620 AF cases). We duplicated the MR analyses using datasets from AF HRC studies and the FinnGen Consortium, and then conducted a meta-analysis which combined the main results. The risk of AF was significantly associated with the genetically determined plasma uridine level (odds ratio [OR] 0.27; 95% confidence interval [CI] 0.16, 0.47; p = 2.39 × 10–6). The association remained consistent in the meta-analysis of the various datasets (OR 0.27; 95% CI 0.17, 0.42; p = 1.34 × 10–8). In conclusion, the plasma uridine level is inversely associated with the risk of AF. Raising the plasma uridine level may have prophylactic potential against AF.

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“…We first performed DrugBank database searches and revealed ISG20 as a UMP target. UMP was demonstrated to possess an anti-fibrillatory effect by activating energy metabolism ( 32 ). Unfortunately, our experiments failed to find UMP-regulated ISG20 expression in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

The regulation of ISG20 expression on SARS-CoV-2 infection in cancer patients and healthy individuals

Cheng

Tan

et al. 2022

Front. Immunol.

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ISG20 inhibits viruses such as SARS-CoV-2 invasion; however, details of its expression and regulation with viral susceptibility remain to be elucidated. The present study analyzed ISG20 expression, isoform information, survival rate, methylation patterns, immune cell infiltration, and COVID-19 outcomes in healthy and cancerous individuals. Cordycepin (CD) and N6, N6-dimethyladenosine (m62A) were used to treat cancer cells for ISG20 expression. We revealed that ISG20 mRNA expression was primarily located in the bone marrow and lymphoid tissues. Interestingly, its expression was significantly increased in 11 different types of cancer, indicating that cancer patients may be less vulnerable to SARS-CoV-2 infection. Among them, higher expression of ISG20 was associated with a long OS in CESC and SKCM, suggesting that ISG20 may be a good marker for both viral prevention and cancer progress. ISG20 promoter methylation was significantly lower in BLCA, READ, and THCA tumor tissues than in the matched normal tissues, while higher in BRCA, LUSC, KIRC, and PAAD. Hypermethylation of ISG20 in KIRC and PAAD tumor tissues was correlated with higher expression of ISG20, suggesting that methylation of ISG20 may not underlie its overexpression. Furthermore, ISG20 expression was significantly correlated with immune infiltration levels, including immune lymphocytes, chemokine, receptors, immunoinhibitors, immunostimulators, and MHC molecules in pan-cancer. STAD exhibited the highest degree of ISG20 mutations; the median progression-free survival time in months for the unaltered group was 61.84, while it was 81.01 in the mutant group. Isoforms ISG20-001 and ISG20−009 showed the same RNase_T domain structure, demonstrating the functional roles in tumorigenesis and SARS-CoV-2 invasion inhibition in cancer patients. Moreover, CD and m62A increase ISG20 expression in various cancer cell lines, implying the antiviral/anti-SARS-CoV-2 therapeutic potential. Altogether, this study highlighted the value of combating cancer by targeting ISG20 during the COVID-19 pandemic, and small molecules extracted from traditional Chinese medicines, such as CD, may have potential as anti-SARS-CoV-2 and anticancer agents by promoting ISG20 expression.

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Antiarrhythmic Effect of Uridine and Uridine-5’-Monophosphate in Acute Myocardial Ischemia

Cited by 9 publications

References 9 publications

The causal effects of genetically determined human blood metabolites on the risk of atrial fibrillation

The causal effects of genetically determined human blood metabolites on the risk of atrial fibrillation

Protective effect of uridine on atrial fibrillation: a Mendelian randomisation study

The regulation of ISG20 expression on SARS-CoV-2 infection in cancer patients and healthy individuals

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