Empagliflozin in acute myocardial infarction reduces no-reflow and preserves cardiac function by preventing endothelial damage
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE255933 | GEO | 2024/09/13
REPOSITORIES: GEO
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Project description:Empagliflozin in acute myocardial infarction reduces no-reflow and preserves cardiac function by preventing endothelial damage
| PRJNA1077267 | ENA
Project description:Glucose-lowering drugs sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of serious heart failure events, regardless of diabetes status, but the underling mechanism of this cardioprotective benefit is unknown. Here, we performed RNA-seq screening in cardiomyocytes to determine the potential cardioprotective mechanism of empagliflozin (EMPA).
2022-12-12 | GSE200598 | GEO
Project description:Ischemic heart failure after acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a trans-valvular axial-flow pump in the LV and delaying myocardial reperfusion, known as Primary Unloading, limits infarct size by reducing LV wall stress and increasing expression of the cardioprotective cytokine, stromal derived factor 1 alpha (SDF1a). The mechanisms underlying the cardioprotective benefit and sustained effect of Primary Unloading remain poorly understood. We now tested the importance of delayed reperfusion, the functional significance of SDF1a, and the late-term impact on myocardial function and scar size associated with Primary Unloading. Adult male swine were subjected to Primary Reperfusion or Primary Unloading after 90 minutes of left anterior descending artery occlusion. Compared to Primary Reperfusion, 30 minutes of Primary Unloading was necessary and sufficient prior to reperfusion to limit infarct size. Primary Unloading was associated with a global shift in gene expression within the infarct zone favoring cardioprotection. Compared to Primary Reperfusion, Primary Unloading for 30 minutes preserved SDF1a protein levels without changing SDF1a mRNA levels within the infarct zone and further promoted a shift towards anti-apoptotic signaling within the infarct zone. Primary Unloading reduced activity levels of proteases known to degrade SDF1a and blocking the SDF1a receptor, CXCR4, attenuated the cardioprotective effect of Primary Unloading. Primary Unloading further reduced LV scar size, improved cardiac function, limited expression of markers associated with heart failure and maladaptive remodeling within the non-infarct zone 28 days after acute myocardial infarction. In conclusion, we introduce that Primary Unloading for 30 minutes before, not after reperfusion limits infarct size, increases SDF1a levels within the infarct zone, and results in a durable reduction in LV scar size, improved cardiac function, and limits markers of heart failure and maladaptive remodeling 28 days after AMI.
2018-10-25 | GSE108644 | GEO
Project description:Restoration of blood flow is the definitive therapy to salvage myocardium following ischemic injury. However, sudden restoration of blood flow to the ischemic myocardium causes ischemia reperfusion injury (IRI). Here, the cardioprotective effect of remote ischemic postconditioning (RPostC) was investigated, based on our in vitro rat model of myocardial IRI. Three groups, including Sham, IRI, and IRI+ RPostC, were utilized for the analysis of Affymetrix Rat Gene 2.0 ST chip.
2019-05-15 | GSE122020 | GEO
Project description:Glucagon-like peptide-1 receptor (GLP-1R) agonists reduce the rates of major cardiovascular events, including myocardial infarction in people with type 2 diabetes, and decrease infarct size while preserving ventricular function in preclinical studies. Nevertheless, the precise cellular sites of GLP-1R expression that mediate the cardioprotective actions of GLP-1 in the setting of ischemic cardiac injury are uncertain. Here, cardiac gene expression profiles regulated by liraglutide were examined using RNA-Seq to interrogate mouse atria and both non-infarcted and non-infarcted ventricular tissue after acute coronary artery ligation.
2022-11-21 | GSE217736 | GEO
Project description:The use of cDNA microarrays has made it possible to analyze expression of thousands of genes simultaneously. We employed microarray gene expression profiling of porcine cDNA to compare myocardial gene expression in infarct core and remote myocardium at 1 week (n=3), 4 weeks (n=3), and 6 weeks (n=3) after surgically induced myocardial infarction (MI) and in sham-operated controls (n=3). More than 8,000 cDNA sequences were identified in myocardium that showed differential expression in response to MI. Different temporal and spatial patterns of gene expression were recognized in the infarct core tissue within this large set of data. Microarray gene profiling revealed candidate genes, some of them described for the first time, which elucidate changes in biological processes at different stages after MI. We evaluated temporal gene expression in a porcine model of myocardial infarction by microarray technology. Nine female pigs (Sus scrofa crossbreed Landrace x Large White) weighing 30-40 kg were subjected to experimental MI by a double-ligation of the first marginal branch of the circumflex artery. Animals were randomly sacrificed at 1 week (n=3), 4 weeks (n=3), or 6 weeks (n=3) after MI. Three paired myocardial samples from the infarct core and remote myocardium were analyzed at each time point. Myocardial samples from sham-operated animals (open-chest cardiac exposure without coronary artery ligation; n=3) were included as physiological controls.
2013-03-01 | E-GEOD-34569 | biostudies-arrayexpress
Project description:SGLT-2 inhibitors, such as empagliflozin, have been shown to reduce the occurrence of cardiovascular events and delay the progression of atherosclerosis. However, its role in atherosclerotic calcification remains unclear. In this research, ApoE-/- mice were fed with western diet and empagliflozin was added to the drinking water for 24 weeks. Empagliflozin treatment significantly alleviated arterial calcification assessed by alizarin red and von kossa staining in aortic roots and reduced the lipid levels, while had little effect on body weight and blood glucose levels in ApoE-/- mice. In vitro studies, empagliflozin significantly inhibits calcification of primary vascular smooth muscle cells (VSMCs) and aortic rings induced by osteogenic media (OM) or inorganic phosphorus (Pi). RNA sequencing of VSMCs cultured in OM with or without empagliflozin showed that empagliflozin negatively regulated the osteogenic differentiation of VSMCs. And further studies confirmed that empagliflozin significantly inhibited osteogenic differentiation of VSMCs via qRT-PCR. Our study demonstrates that empagliflozin alleviates atherosclerotic calcification by inhibiting osteogenic differentiation of VSMCs, which addressed a critical need for the discovery of a drug-based therapeutic approach in the treatment of atherosclerotic calcification.
2023-11-22 | GSE243752 | GEO
Project description:Mononuclear phagocytes promote injury and repair following myocardial infarction but discriminating functions within mixed populations remains challenging. We utilized fate mapping and single cell RNA-sequencing to delineate fate specification trajectories of heterogeneous cardiac macrophage subpopulations. In steady state, TIMD4 expression tracked with a dominant resident cardiac macrophage subset that persisted via in situ self-renewal with minimal monocyte input. Following ischemic injury, monocytes displayed significant plasticity, ultimately adopting transcriptional states similar to resident macrophages, but also multiple unique states. Ischemic injury reduced resident macrophage abundance within infarct tissue, and despite transcriptional similarity, TIMD4 expression distinguished resident from recruited macrophages. Specific lineage-based depletion of resident cardiac macrophages resulted in depressed cardiac function and adverse remodeling primarily within the peri-infarct zone, the only region of the myocardium where resident macrophages expanded numerically following injury. Together, these data highlight a non-redundant, cardioprotective role of resident cardiac macrophages, and the diverse transcriptional fates recruited monocytes can adopt.
2018-12-15 | GSE119355 | GEO
Project description:Ischemia reperfusion injury (IRI) following intervention for myocardial infarction remains an unmet clinical problem. Using an established mouse model, we demonstrated that IRI induces multiple cardiac cell linages to senescence. Senescence is is detrimental to recovery, as treatment with the senolytic navitoclax improves functional recovery.Here we are using SWATH-MS to investigate the molecular mechanisms responsible for the effect of navitoclax treatment.
2020-02-29 | MSV000085040 | MassIVE
Project description:The Murphy Roth Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high post-myocardial infarction (MI) survival rate compared with C57BL6/J (C57) mice. The biological processes responsible for this survival advantage are unknown. We compared acute post-MI gene expression in C57 and MRL hearts using microarrays and identified promising candidate biological processes underlying increased survival in the MRL. Hearts from both strains were excised at different time points before or after MI for RNA extraction and hybridization to MOE430A arrays. Baseline hearts were excised from healthy mice that had not undergone the MI procedure (day 0). Infarct tissue in this case means tissue taken from the anterior-apical region that would be the infarct region in a post-MI heart. Non-infarct covers the remainder of the LV. Post-MI hearts were excised either 1 or 5 days after MI. We had successful hybridizations for 3 replicates each of C57 day 0 infarct and non-infarct tissue (6 arrays), 4 MRL day 0 infarct and non-infarct tissue (8 arrays), 4 C57 day 1 infarct and non-infarct tissue (8 arrays), 4 MRL day 1 infarct and non-infarct tissue (8 arrays), 4 C57 day 5 infarct and non-infarct tissue (8 arrays), and 4 MRL day 5 infarct and non-infarct tissue (8 arrays).
2010-05-27 | E-GEOD-19322 | biostudies-arrayexpress