Expression data from healthy and diastolic heart failure rats
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PROVIDER: PRJNA520901 | ENA |
REPOSITORIES: ENA
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Project description:Heart failure (HF) with preserved ejection fraction (HFpEF) is rising, whose morbidity, mortality and healthcare costs are similar to HF with reduced ejection fraction (HFrEF). Although substantial molecular pathways lead to the changes in organ and tissue levels, there are still lack of successful treatments for HFpEF given the complexity molecular networks remaining unknown. Here we report that the significantly changed genes of HFpEF rats associates positively with inflammatory processes and immune responses while negatively with calcium ion transport into cytosol. GSEA analysis shows several KEGG pathways are significantly enriched in HFpEF rats including p53 signaling pathway, Toll like receptor signaling pathway and so on. Our study provides new insights into HFpEF pathogenesis and a new therapeutic against HFpEF.
2019-02-05 | GSE126062 | GEO
Project description:Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are yet unknown. Research is hampered by the lack of a good RVF model. Our aim was to study the pathophysiology of RVF in a rat model of chronic pressure load. Wistar rats (n=19) were subjected to pulmonary artery banding (PAB, 1.1mm) or sham surgery (CON). All PAB rats developed RVF (reduced cardiac output, RV stroke volume, TAPSE, increased end diastolic pressure, all p<0.05 vs. CON) but clinical symptoms of RVF (inactivity, ruffled fur, dyspnea, ascites) necessitating termination ensued in a subset (5/12) of rats (RVF+) after a period of 52±5 days. Rats with RVF+ had significantly worse RV function and pericardial effusion and liver congestion compared to RVF rats without symptoms (all p<0.05), despite similar pressure load (p=NS RVF vs. RVF+). Chronic pulmonary artery banding invariably leads to RV failure in rats, and a subset transitions to advanced clinical RVF. RVF is characterized by enhanced contractility, progressive diastolic dysfunction and derangement of energy metabolism, thus improving diastolic function and targeting RV metabolism may be the keys to treating RVF. Total RNA optainded ( Heart) of 7 Controls ,5 RVF+ and 4 RVF samples where used for this array study
2014-12-08 | E-GEOD-46863 | biostudies-arrayexpress
Project description:Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are yet unknown. Research is hampered by the lack of a good RVF model. Our aim was to study the pathophysiology of RVF in a rat model of chronic pressure load. Wistar rats (n=19) were subjected to pulmonary artery banding (PAB, 1.1mm) or sham surgery (CON). All PAB rats developed RVF (reduced cardiac output, RV stroke volume, TAPSE, increased end diastolic pressure, all p<0.05 vs. CON) but clinical symptoms of RVF (inactivity, ruffled fur, dyspnea, ascites) necessitating termination ensued in a subset (5/12) of rats (RVF+) after a period of 52±5 days. Rats with RVF+ had significantly worse RV function and pericardial effusion and liver congestion compared to RVF rats without symptoms (all p<0.05), despite similar pressure load (p=NS RVF vs. RVF+). Chronic pulmonary artery banding invariably leads to RV failure in rats, and a subset transitions to advanced clinical RVF. RVF is characterized by enhanced contractility, progressive diastolic dysfunction and derangement of energy metabolism, thus improving diastolic function and targeting RV metabolism may be the keys to treating RVF.
2014-12-08 | GSE46863 | GEO
Project description:As part of genetic studies of heart failure in mice, we observed that heart mitochondrial DNA levels and function tend to be reduced in females as compared to males. We also observed that expression of genes encoding mitochondrial proteins were higher in males than females in human cohorts. Heart failure with preserved ejection fraction (HFpEF) exhibits a sex bias, being more common in women than men, and we hypothesized that mitochondrial sex differences might underlie this bias. We tested this in a panel of genetically diverse inbred strains of mice, termed the Hybrid Mouse Diversity Panel (HMDP). Indeed, we found that mitochondrial gene expression was highly correlated with diastolic function, a key trait in HFpEF. Consistent with this, studies of a “two-hit” mouse model of HFpEF confirmed that mitochondrial function differed between sexes and was strongly associated with a number of HFpEF traits. By integrating data from human heart failure and the mouse HMDP cohort, we identified the mitochondrial protein Acsl6 as a genetic determinant of diastolic function. We validated its role in HFpEF using adenoviral over-expression in the heart. We conclude that sex differences in mitochondrial function underlie, in part, the sex bias in diastolic function.
2022-01-31 | GSE194151 | GEO
Project description:Background: Atrial fibrillation (AF) is commonly associated with diastolic dysfunction. Both conditions involve overactivation of inflammatory signaling and cardiac fibroblasts (FBs). While the activation of the NLRP3-inflammasome in cardiomyocytes is known to cause atrial electrical remodeling and arrhythmogenicity, the role of FB NLRP3-inflammasome in heart disease is unknown. Objectives: We aimed to elucidate the contribution of FB-specific NLRP3-inflammasome activation to cardiac function and arrhythmogenesis. Methods: Human atrial FBs were isolated from atrial biopsies of AF and sinus rhythm patients. We established an FB-specific knockin (FB-KI) mouse model with FB-restricted expression of constitutively active NLRP3. Cardiac function and AF susceptibility were assessed through echocardiography, tissue Doppler, programmed electrical stimulation, and optical mapping. Results: NLRP3 and IL1B were upregulated in atrial FBs of patients with persistent AF. FB-KI mice exhibited enlarged left atria, enhanced AF-susceptibility, and heart failure with diastolic dysfunction. FBs from FB-KI mice were more transdifferentiated, migratory, and proliferative than those from control. FB-KI mice showed increased fibrous content in both atria and ventricles, atrial gap junction remodeling, and reduced atrial conduction velocity. Single-nuclei RNA-seq analysis revealed prominent transcript remodeling of metabolic pathways across multiple cell types, enhanced extracellular matrix signaling, and altered intercellular communications. Knockdown of Nlrp3 in FBs via adeno-associated virus type-dj/8 mediated transfer of shRNA reduced AF-susceptibility and prevented cardiomyopathy in FB-KI mice. Conclusions: FB-restricted activation of the NLRP3-inflammasome promotes cardiac fibrosis and AF-susceptibility. This study identifies the FB NLRP3-inflammasome activation as a key mechanism governing the concomitant AF and heart failure with diastolic dysfunction.
2025-05-09 | GSE218250 | GEO
Project description:We aimed to identify gene variants associated with heart failure by using a rat model of the human disease. We performed invasive cardiac hemodynamic measurements in F2 crosses between spontaneously hypertensive heart failure rats (SHHF) and reference strains. We combined linkage analyses with genome-wide expression profiling .
2008-09-01 | E-TABM-418 | biostudies-arrayexpress
Project description:Rats overexpressing the human renin and angiotensinogen genes die after seven weeks of end organ damage. They develop hypertension, heart hypertrophy and proteinuria.We compared terminal heart failure, these are indeed terminally ill to double transgenic animals suffering on hypertension, proteinuria and heart hypertrophy. In addition, Losartan-treated animals (10 mg/kg/d)showed similar physiological parameters (normotension, no proteinuria and no heart hypertrophy compared to control sprague dawley rats.
2008-06-11 | E-GEOD-1557 | biostudies-arrayexpress
Project description:Heart Failure Network - Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (HFN RELAX-BioLINCC)
| PRJNA1079431 | ENA
Project description:Heart Failure Network - Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (HFN RELAX-BioLINCC)
| PRJNA1079432 | ENA
Project description:Fibroblast-restricted inflammasome activation promotes atrial fibrillation and heart failure with diastolic dysfunction
| PRJNA902802 | ENA