Optimized alternative ordering of dapagliflozin and sacubitril-valsartan in post-myocardial infarction heart failure
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PROVIDER: PRJNA953047 | 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:Purpose: To get insight into mouse strain-dependent differences in vascular remodeling, we analyzed gene expression profiles of the ligated carotid arteries after interventions in C57BL/6J and 129X1/SvJ mice Methods: mRNA isolations from snap-frozen single carotids (n=3 per group) were conducted. Tissue homogenization by Next Advance Bullet Blender with zirconium oxide beads and Trizol. Total RNA isolation using Trizol and Qiagen RNeasy Micro kit. Results: Multiple quality controls showed a reliable RNAseq of mRNAs from the ligated carotid arteries. Specifically, there was less than 2.6% drop in reads that ranged between 26.5 to 37.7 million reads. We found a good alignment and mapping to a mouse genome (82.4 - 91.0%) in this RNAseq study. A differential gene expression analysis was done by DESeq2-1.16.1 within R-3.4.1 for data normalization and differential expression analysis with an adjusted p-value threshold of 0.05 on each set of raw expression measures. Conclusions: Our study shows significant differences in gene expression signatures in carotid arteries from two inbred mouse strains after sacubitril/valsartan treatment. We conclude that genetic background determines efficacy of the sacubitril/valsartan in mice.
2020-04-10 | GSE129689 | GEO
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:RNA sequencing of mouse carotid arteries after sacubitril/valsartan treatment
| PRJNA532452 | ENA
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:The specific mechanism of sodium-glucose cotransporter 2 (SGLT2) inhibitor in heart failure (HF) needs to be elucidated. In this study, we use SGLT2 global knockout (SGLT2-KO) mice to assess the mechanism of SGLT2 inhibitor on HF. Dapagliflozin ameliorates both myocardial infarction (MI)-and transverse aortic constriction (TAC) -induced HF. Global SGLT2-deficiency doesn’t exert protection against adverse remodeling in both MI- and TAC-induced HF models. Dapagliflozin blurs MI- and TAC-induced HF phenotypes in SGLT2-KO mice. Dapagliflozin causes major changes in cardiac fibrosis and inflammation. Based on single-cell RNA sequencing dapagliflozin causes significant differences in the gene expression profile of macrophages and fibroblasts. Moreover, dapagliflozin directly inhibites macrophage inflammation, thereby suppressing cardiac fibroblasts activation. The cardio-protection of dapagliflozin is blurred in mice treated with a C-C chemokine receptor type 2 (CCR2) antagonist. Taken together the protective effects of dapagliflozin against HF are independent of SGLT2, macrophage inhibition is the main target of dapagliflozin against HF.
2023-11-14 | GSE247062 | GEO
Project description:tRNA-derived Small RNAs and their Potential Roles in the Therapeutic Heterogeneity of Sacubitril/valsartan in Heart Failure Patients after Acute Myocardial Infarction
| PRJNA857580 | ENA
Project description:We show the proximal tubular specific pathway analysis demonstrating the downregulation of oxidative phosphorylation in dapagliflozin treated db/db mice, a type 2 diabetic model. After 8-week treatment of dapagliflozin for db/db mice having proximal tubule specific tdTomato reporter, tdTomato-positive cells were isolated by FACS. Pathway analysis of RNA sequence of isolated tubular epithelia revealed that oxidative phosphorylation was downregulated in dapagliflozin-treated mice. However, depletion of renal tissue ATP content in db/db mice was ameliorated by dapagliflozin administration. Pimonidazole staining demonstrated that renal cortical tissue hypoxia was noted in db/db mice, which was improved by dapagliflozin administration. These findings suggest that dapagliflozin can ameliorated the excessive oxygen and ATP consumption and subsequent tissue hypoxia in diabetic kidney, which may explain, in part, the responsible mechanisms of renoprotecitive effect by dapagliflozin.
2022-09-28 | GSE185801 | GEO