Analysis of differential genes in myocardial hypertrophy mice treated with dapagliflozin
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PROVIDER: PRJNA759225 | ENA |
REPOSITORIES: ENA
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Project description:The purpose of this study was to investigate the effect of dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, on relieving cardiac hypertrophy and its potential molecular mechanism. Dapagliflozin activated the Plin5/PPARα signaling axis and exerts a protective effect against cardiac hypertrophy.
2021-09-01 | GSE183120 | GEO
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: Although myocardial hypertrophy is an essential component of heart’s response to many forms of stress, prolonger excessive hypertrophy contributes importantly to the pathogenesis of heart disease. The pimobendan is a drug that both inhibits phosphodiesterase 3 (PDE3) and acts as a calcium sensitizer, which has been used to treat heart failure. The effects of pimobendan on myocardial hypertrophy is controversial. Objective: This study aims to evaluate the therapeutic effect of pimobendan on myocardial hypertrophy. Methods: Mice were treated with low oral doses of pimobendan (1mg/kg/d) for 4 weeks after transaortic constriction. Heart structure and function was assessed using ultrasound, hemodynamic measurements and histology combined with biochemical assessments of myocardial hypertrophy. We also examined the effects of pimobendan (100 µM) on hypertrophy in cultured neonatal rat cardiomyocytes (NRCMs) induced by 50 µM phenylephrine (PE). Results: The doses pimobendan used in our studies had no effect on baseline contractility. Nevertheless, pimobendan administration of mice subjected to TAC decreased heart weights (normalized to either tibia length or body weight) ventricular wall thickness, cardiomyocyte sizes, myocardial fibrosis and the levels of a number of key myocardial hypertrophy markers (WHICH ONES). In cultured neonatal cardiomyocytes, pimobendan attenuated the PE-induced hypertrophy. In both hypertrophy models pimobendan reduced the phosphorylation levels of several essential proteins in the MAPK pathway, PI3K-AKT pathway, and calcineurin signaling pathway. Conclusion: Low pimobendan may attenuate myocardial hypertrophy. Although the underlying mechanisms remain to be elucidated, the MAPK pathway is likely to play a role.
2023-07-01 | GSE182501 | GEO
Project description:SIRT5 is one of the seven members of the NAD+-dependent sirtuin family of protein deacylase that is mainly present in mitochondria and regulates metabolism. In heart, SIRT5 is highly expressed and responsible for succinylation on metabolic enzymes. Although the role of SIRT5 in maintaining cardiac homeostasis under physiological stress and few potential substrates of SIRT5 have been preliminarily revealed, the regulatory network and key cellular signaling pathways involving SIRT5 in myocardial hypertrophy remain largely unknown. Here, we used an established murine model of pressure overload-induced myocardial hypertrophy caused by transverse aortic constriction (TAC) to outline the network and pathway involving SIRT5 in cardiac stress responses. Remarkably, SIRT5 KO mice had enhanced myocardial hypertrophy after TAC surgery compared with wild-type mice.
2024-10-05 | GSE186985 | GEO
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
Project description:tRNA-derived fragments (tRFs) have served as new class of non-coding RNA and played important role in regulating cellular RNA processing and protein translation, which was also proved have function on the intergenerational effects of paternal disease. However, there was no study reported the influence of tRFs on myocardial hypertrophy. In the current study, we explore the hypothesis that tRFs in response to myocardial hypertrophy and contribute to intergenerational inheritance.We used isoproterenol induced myocardial hypertrophy rat model. Small RNA (< 40 nt) tanscriptome sequencing was used to select differential expressed tRFs. We over-expressed the highest foldchange tRFs on H9c2 cell to check its function in enlarging cardiocytes surface area. We also compared the tRFs expression pattern in F0 sperm and F1 offspring heart between myocardial hypertrophy (Hyp) and control group (Con), as well as evaluated the phynotype of myocardial hypertrophy in F1 offspring. ISO successfully induced a typical cardiac hypertrophy model in our study. Small RNA-seq revealed tRFs were extremely enriched (84%) in Hyp heart. Overexpression tRFs1 and tRFs2 would both enlarge the surface area of cardiac cell and increase hypertrophic markers (ANF, BNP, and β-MHC) expression. tRFs1, tRFs2, tRFs3 and tRFs4 were also significantly high expressed in Hyp F0 sperm and in Hyp F1 offspring heart, but no function of tRFs7, tRFs9 and tRFs10. Compared to Con F1 offspring, Hyp F1 offspring had high expression levels of β-MHC and ANP genes, and increased fibrosis levles and apoptotic cell in heart.We demonstrate that tRFs are involved in regulating the response of myocardial hypertrophy, it might serve as novel epigenetic factor and contribute to intergenerational inheritance of cardiac hypertrophy.
2017-11-04 | GSE106511 | GEO
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:Background: Exercise can induce physiological myocardial hypertrophy (PMH), and former athletes can live 5-6 years longer than nonathletic controls, suggesting a benefit after regression of PMH. We previously reported that regression of pathological myocardial hypertrophy has antihypertrophic effects. Accordingly, we hypothesized that antihypertrophic memory exists even after PMH has regressed, increasing myocardial resistance to subsequent pathological hypertrophic stress. Methods and Results: C57BL/6 mice were submitted to 21 days of swimming training to develop PMH. After termination of exercise, PMH regressed within 1 week. PMH regression mice (hypertrophic preconditioning group, EHP) and sedentary mice (control group) then underwent transverse aortic constriction (TAC) or a sham operation. At 1 and 4 weeks after TAC, the EHP group showed less increase in myocardial hypertrophy and lower expression of the Nppa and Myh7 genes than the sedentary group. At 4 weeks after TAC, EHP mice had less pulmonary congestion, smaller left ventricular dimensions and end-diastolic pressure, and a larger left ventricular ejection fraction and maximum pressure change rate than sedentary mice. Quantitative polymerase chain reaction (qPCR) revealed that the long noncoding myosin heavy chain associated RNA transcript Mhrt779 was one of the markedly upregulated long noncoding RNAs in the EHP group. Silencing of Mhrt779 attenuated the antihypertrophic effect of EHP in mice with TAC and in cultured cardiomyocytes treated with angiotensin II, and overexpression enhanced the antihypertrophic effect. By chromatin immunoprecipitation assay and qPCR, we found that EHP increased histone 3 trimethylation (H3K4me3 and H3K36me3) at a4 promoter of Mhrt779. Comprehensive identification of RNA-binding proteins by mass spectrometry and Western blot showed that Mhrt779 can bind Brg1 to upregulate Hdac2 and inhibit phosphorylation of Akt and GSK3β. Conclusions: Myocardial hypertrophy preconditioning evoked by exercise increases resistance to pathological stress via an antihypertrophic effect mediated by a signal pathway of Mhrt779 /Hdac2/p-Akt/p-GSK3β.
2020-11-07 | GSE161030 | GEO
Project description:Role of SIRT5 in Inhibition of Myocardial Hypertrophy
| PRJNA777232 | ENA
Project description:To explore the pathogenesis of myocardial hypertrophy, Proteomic Analysis was performed to identify the differentially expressed proteins in the human myocardial tissues of non-hypertrophic control and myocardial hypertrophy patients. We used echocardiography to detect the thickness of the ventricular septum in patients undergoing heart valve replacement surgery .The thickness of the ventricular septum over 11mm is defined as myocardial hypertrophy of patients, those less than or equal to 11mm were considered as non-hypertrophic controls. We collected a total of 6 cases of non-hypertrophic controls and 6 cases of myocardial hypertrophy patients' myocardial tissues, and Proteomic Analysis was performed by mass spectrometry.
2021-06-14 | PXD023778 | Pride