TRNA-derived Small RNAs and their Potential Roles in the Therapeutic Heterogeneity of Sacubitril/valsartan in Heart Failure Patients after Acute Myocardial Infarction
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PROVIDER: PRJNA857580 | ENA |
REPOSITORIES: ENA
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Project description:We tested it in an animal model of myocardial infarction to ensure whether early initiation of dapagliflozin (DAPA), or different orders of combination with sacubitril-valsartan would result in a greater improvement of heart function than sacubitril-valsartan alone in post-myocardial infarction heart failure.
2023-04-13 | GSE229147 | GEO
Project description:Background: It has been reported that sacubitril/valsartan can improve cardiac function in acute myocardial infarction (AMI) patients complicated by heart failure (HF). However, a number of patients cannot be treated successfully; this phenomenon is called sacubitril/valsartan resistance (SVR), and the mechanisms remain unclear. Methods:In our present research, the expression profiles of tRNA-derived small RNAs (tsRNAs) in SVR along with NSVR patients were determined by RNA sequencing. Through bioinformatics, qRT–PCR, and cell-based experiments, we identified SVR-related tsRNAs and confirmed their diagnostic value, predicted their targeted genes, and explored the enriched signal pathways as well as regulatory roles of tsRNAs in SVR. Results:Our research indicated that 36 tsRNAs were upregulated and that 21 tsRNAs were downregulated in SVR. Among these tsRNAs, the expression of tRF-59:76-Tyr-GTA-2-M3 and tRF-60:76-Val-AAC-1-M5 was upregulated, while the expression of tRF-1:29-Gly-GCC-1 was downregulated in the group of SVR. Receiver operating characteristic (ROC) curve analysis demonstrated that these three tsRNAs were potential biomarkers of the therapeutic heterogeneity of sacubitril/valsartan. Moreover, tRF-60:76-Val-AAC-1-M5 might target Tnfrsf10b and Bcl2l1 to influence the observed therapeutic heterogeneity through the lipid and atherosclerosis signaling pathways. Conclusions:Hence, tsRNA might play a vital role in SVR. These discoveries provide new insights for the mechanistic investigation of responsiveness to sacubitril/valsartan.
2022-10-19 | GSE207882 | GEO
Project description:Comprehensive analysis of the RNA transcriptome expression profiles and construction of the ceRNA network in heart failure patients with therapeutic heterogeneity of sacubitril/valsartan after acute myocardial infarction Patients after Acute Myocardial Infarction Sacubitril/valsartan has a noteworthy advantage in improving ventricular remodelling, as well as reducing cardiovascular mortality and the rate of heart failure (HF) readmission. However, clinically, some patients with HF still have low sensitivity to sacubitril/valsartan, indicating sacubitril/valsartan resistance (SVR).
2022-12-31 | GSE212181 | GEO
Project description:Optimized alternative ordering of dapagliflozin and sacubitril-valsartan in post-myocardial infarction heart failure
| PRJNA953047 | ENA
Project description:To find which genes were significantly modulated by Valsartan in non-infarcted left ventricle, 4 weeks after coronary artery ligation, and to correlate emerging modulated pathways with histology and cardiac magnetic resonance (CMR) imaging. The goal was to validate the estimation of the systolic dysfunction and of the regions preserved by pharmacological treatment performed with a CMR index. Title of the associated submitted paper: Evaluation of left ventricle function by regional fractional area change (RFAC) in a mouse model of myocardial infarction secondary to Valsartan treatment. Abstract: Purpose: Left ventricle (LV) regional fractional area change (RFAC) measured by cardiac magnetic resonance (CMR) allows the non-invasive localization and quantification of the extent of myocardial infarction (MI), and could be applied to assess the effectiveness of pharmacological or regenerative therapies. Here we investigate the ability of RFAC to identify regional dysfunction and discriminate the effect of pharmacological treatment with valsartan, a selective antagonist of angiotensin II type 1 receptor, in a model of MI. Methods: C57BL/6N mice, undergoing coronary artery ligation, were divided into two groups: untreated (MI) or treated with Valsartan (MI+Val). Sham-operated mice were used as a control. Cardiac dimensions and function were assessed at baseline, 24 hours, 1 and 4 weeks post surgery by CMR and echocardiography. At sacrifice histology and whole-genome gene expression profiling were performed. Results: RFAC was able to detect significant differences between treatment groups whereas the global ejection fraction was not. RFAC showed greater loss of contractility in remote non-infarcted myocardium in MI group than in MI+Val group. Consistently, in the same region MI+Val mice showed reduced myocyte hypertrophy, fibroblast proliferation, and fibrosis and modulation of target genes; in addition, left atrium volumes, appendage length and duct contractility were preserved. Conclusion: In this study, RFAC effectively estimated the degree of systolic dysfunction and discriminated the regions preserved by pharmacological treatment. RFAC index is a promising tool to monitor changes in LV contractility and to assess the effectiveness of therapeutic regimens in clinical settings.
2015-09-30 | GSE68426 | GEO
Project description:As one of the major cardiovascular diseases, myocardial infarction is the most serious manifestation of coronary artery disease, which has attracted wide attention due to its high morbidity and mortality. The left anterior descending artery(LAD) of 6-8 weeks old male KM mice was ligated for 40min, followed by perfusion to establish an ischemia-reperfusion(I/R) model. After 3 days of monitoring, 60 mg/kg sacubitril/valsartan sodium was given for a week. Hematoxylin-eosin(HE) staining, 2, 3, 5-triphenyl-tetrazolium chloride(TTC) staining and echocardiography were used to evaluate the therapeutic effect of sacubitril/valsartan sodium on I/R.The proteomics information of heart tissue was obtained by data-independent acquisition(DIA) proteomics. The analysis results showed that sacubitril/valsartan sodium may mediate the treatment of I/R injury by regulating enzyme activity and immune-related biological processes, up-regulating fatty acid degradation metabolic pathway, PPAR pathway, peroxisome pathway, and down-regulating complement system and ribosome pathway.The results showed that sacubitril/valsartan sodium had a good therapeutic effect on I/R injury.
2023-09-04 | PXD045090 |
Project description:We demonstrate an age-independent loss of type H bone endothelium in heart failure after myocardial infarction in both mice and in humans. Using single-cell RNA sequencing, we delineate the transcriptional heterogeneity of human bone marrow endothelium showing increased expression of inflammatory genes, including IL1B and MYC, in ischemic heart failure. Endothelial-specific overexpression of MYC was sufficient to induce type H bone endothelial cells, whereas inhibition of NLRP3-dependent IL-1 production partially prevents the post-myocardial infarction loss of type H vasculature in mice.
2021-05-13 | E-MTAB-10448 | biostudies-arrayexpress
Project description:We demonstrate an age-independent loss of type H bone endothelium in heart failure after myocardial infarction in both mice and in humans. Using single-cell RNA sequencing, we delineate the transcriptional heterogeneity of human bone marrow endothelium showing increased expression of inflammatory genes, including IL1B and MYC, in ischemic heart failure. Endothelial-specific overexpression of MYC was sufficient to induce type H bone endothelial cells, whereas inhibition of NLRP3-dependent IL-1 production partially prevents the post-myocardial infarction loss of type H vasculature in mice.
2021-05-11 | E-MTAB-10432 | biostudies-arrayexpress
Project description:Affymetrix microarray analysis of molecular changes after myocardial infarction. Samples of heart tissue were analyzed after myocardial infarction from WT and reg3beta knock-out mice. Samples from scar tissue and samples adjacent to the scar were analyzed. In the experiment we primarily compared infarction zone of wild-type to infarction zone of knock-out animals, and remote zone of wild-type to remote zone of knock-outs.
2015-06-29 | E-MTAB-2561 | biostudies-arrayexpress
Project description:Despite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI) is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients. ST-segment elevation myocardial infarction alters expression of several groups of genes. On admission, several genes and pathways that could be directly or indirectly linked with lipid/glucose metabolism, platelet function and atherosclerotic plaque stability were affected (signaling of PPAR, IL-10, IL-6). Analysis at discharge highlighted specific immune response (upregulation of immunoglobulins). Highly significant and substantial upregulation of SOCS3 and FAM20 genes expression in the first 4-6 days of myocardial infarction in all patients is the most robust observation of our work Twenty-eight patients with ST-segment elevation myocardial infarction (STEMI) were included. The blood was collected on the 1st day of myocardial infarction, after 4-6 days, and after 6 months. Control group comprised 14 patients with stable coronary artery disease (CAD), without history of myocardial infarction. Gene expression analysis was performed with Affymetrix GeneChipM-BM-. Human Gene 1.0 ST microarrays and GCS3000 TG system.
2014-10-23 | E-GEOD-62646 | biostudies-arrayexpress