scholarly journals Epitranscriptomics of Ischemic Heart Disease—The IHD-EPITRAN Study Design and Objectives

2021 ◽  
Vol 22 (12) ◽  
pp. 6630
Author(s):  
Vilbert Sikorski ◽  
Pasi Karjalainen ◽  
Daria Blokhina ◽  
Kati Oksaharju ◽  
Jahangir Khan ◽  
...  

Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as N-6-methyl-adenosine (m6A) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on m6A and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of m6A and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y A Dyleva ◽  
O Gruzdeva ◽  
E Uchasova ◽  
D Borodkina ◽  
E Belik ◽  
...  

Abstract Obesity is still a major health, social and economic problem throughout the world. Recently, it is important to study the role of adipokines of adipose tissue of various localization in the development of cardiovascular diseases, as well as methods for their pharmacological correction. Purpose The study was to evaluate the effect of rosuvastatin on the secretion of leptin and its receptor by adipocytes of different localization, as well as on the expression of their genes in patients with ischemic heart disease. Methods 29 patients with coronary heart disease which will be held coronary bypass surgery. Adipocytes were isolated from the samples of SAT, EAT and PVAT obtained during coronary artery bypass grafting, which were cultured for 24 hours with rosuvastatin 1 μmol/l and 5 μmol/l. A day later, the concentration of leptin and the leptin receptor in cell culture was determined. All study was carried out in compliance with the Helsinki Declaration, and its protocol was approved by the Ethical Committee of Research Institute. Statistical analysis was performed using Statistica 10.0. All patients gave written informed consent to participate in the study. Results 1 μmol/l of rosuvastatin increased the level of leptin 1.6 and 2.9 times higher in adipocytes SAT compared with EAT and PVAT, respectively, and 1.8 times higher in EAT than in PVAT, which is consistent with the results of expression leptin gene. The concentration of rosuvastatin 5 μmol/l had an effect only on adipocytes SAT, increasing the level of leptin 1.6 and 2.2 times in comparison with adipocytes EAT and PVAT. Rosuvastatin had no significant effect on leptin receptor soluble levels. The free leptin index was higher in adipocytes SAT in the presence of 1 μmol/l of rosuvastatin 1.6 and 2.8 times in comparison with adipocytes of EAT and PVAT. Conclusion The concentration of rosuvastatin 1 μmol/l had a more pronounced effect on adipocytes compared to a concentration of 5 μmol/l and increased the level of leptin and its expression in cell culture. At the same time, a high content of leptin under conditions of low expression of a soluble receptor to leptin in the presence of rosuvastatin 1 μmol/l can lead to leptin resistance, more pronounced in SAT adipocytes.


2015 ◽  
Vol 2 (4) ◽  
pp. 192-197 ◽  
Author(s):  
Shibban K Kaul ◽  
Archit Pankaj Patel ◽  
Jayant N Karbhase ◽  
Rajiv Kumar Srivastava ◽  
Sameer Sudhirchandra Kadam ◽  
...  

2019 ◽  
Vol 64 (9) ◽  
pp. 516-524
Author(s):  
A. A. Zhloba ◽  
T. F. Subbotina ◽  
N. S. Molchan ◽  
Yu. S. Polushin

The level of homoarginine (hArg) in terms of prognostic significance may exceed the natriuretic peptides and other well-known markers according to the latest data about the progression of cardiovascular diseases. The lack of data on the association of hArg levels with levels of other metabolites makes it difficult to understand its role in the pathogenesis of cardiovascular diseases. Relationships of hArg and other amino acids, including methionine (Met) and total homocysteine (tHcy), and their ratio in patients with ischemic heart disease were evaluated. The study included 74 patients with coronary heart disease (57 men and 17 women) aged 62 (57 - 67) years before coronary artery bypass surgery and 27 healthy people of similar age. In patients, the level of hArg was almost 2 times lower (p <0.05) than in healthy individuals and rates lower than 1.4 μM were in half of them. The statistically significant decrease (p = 0.0025) of the Met/tHcy ratio corresponded to a decrease in the level of hArg. This ratio did not correlate with glucose level or body mass index. Less statistical significance of hArg correlation with levels of Met or tHcy separately was observed. In the subgroup of patients with hAarg level above 2.1 μM, a lower incidence of myocardial infarction was noted. Thus, a low hArg level is associated with impaired metabolism of sulfur-containing amino acids involved in transmethylation reactions, in patients with ischemic heart disease. The Met/tHcy ratio, closely correlating with the level of hArg, apparently reveals a link between the reactions of creatine formation and transmethylation, highlighting a cohort of patients with the most profound and dangerous changes in tissue metabolism.


Kardiologiia ◽  
2019 ◽  
Vol 59 (6) ◽  
pp. 12-17
Author(s):  
O. L. Barbarash ◽  
V. V. Kashtalap ◽  
M. V. Zykov ◽  
O. N. Hryachkova ◽  
I. A. Shibanova

Purpose: to assess drug therapy and achievement of target parameters of treatment in patients with ischemic heart disease (IHD) during 3–5 years of follow-up aſter coronary bypass surgery.Materials and methods. From the initial sample of the coronary bypass surgery registry (n=680) we selected for this study 111 men (mean age 61 [55; 65] years) hospitalized in 2011 with clinical picture of IHD for coronary artery bypass graſting (CABG).Results. Mean duration of follow-up was 4.2 years. Mortality was 11.7 % (n=13), 11 deaths were cardiovascular, 2 – from unknown causes. End points defined as repeat hospitalizations and IHD progression were registered in 18 of 98 patients (18.4 %). Only in 25 % of patients during 3–5 years of observation aſter CABG there were no clinical signs of angina. Five patients (5.1 %) developed new type 2 diabetes. Drug therapy: 80 patients (81.6 %) received acetylsalicylic acid, 60 (61.2 %) – angiotensin converting enzyme inhibitors, 80 (81.6 %) – β-adrenoblockers. Eighty-one men (82.6 %) received statins, but only 20 of 98 re-examined patients (20.4 %) took high doses. Target levels of low density lipoprotein cholesterolConclusion. Data of clinical practice illustrate insufficient quality of basic and antianginal therapy in patients with IHD aſter CABG. Indicators of control of angina, heart rate, achievement of target levels of parameters of lipid metabolism remain unsatisfactory.


2015 ◽  
Vol 17 (2) ◽  
pp. 18
Author(s):  
O. V. Petrova ◽  
D. G. Tarasov ◽  
A. P. Motreva ◽  
Yu. B. Martyanova ◽  
A. V. Kadykova ◽  
...  

Dynamics of N-terminal natriuretic propeptide (NT-proBNP) and troponin T in the blood of patients with ischemic heart disease after CABG on a beating heart is studied. It is found out that the level of NT-proBNP in patients with ischemic heart disease at admission correlates with their functional class, left ventricular ejection fraction and end-diastolic volume). It is also shown that the level of NT-proBNP increases in 1 day after CABG and reaches the maximum values in3 days. At the 15th day a decrease in the level of NT-proBNP is observed, however, which reaches the baseline values. The analysis of correlation between NT-proBNP and troponin Т has revealed an inverse correlation between the indicators under study, which testifies to the fact that NT-proBNP cannot be used as a myocardial injury marker in patients with ischemic heart disease after CABG.


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