Transcriptomic responses of the kidney to development of and recovery from acute decompensated heart failure (ADHF)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE180502 | GEO | 2021/09/19
REPOSITORIES: GEO
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Project description:A quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI), an abrupt loss of kidney function that doubles the risk of death at one-year. There is a critical need to identify early markers for AKI in ADHF, however, no protein candidates have been validated as diagnostic or prognostic biomarkers in this setting. We aimed to identify novel candidate protein biomarkers by quantifying changes in protein expression in the kidney that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using Sequential Window Acquisition of All Theoretical Mass Spectrometry (SWATH-MS) in kidney cortex from healthy control sheep (n=5), sheep with established rapid pacing-induced ADHF (n=8) and sheep after ~4 weeks recovery from ADHF (n=7). Of 790 proteins quantified, we identified 17 candidate kidney injury markers, one potential marker of kidney recovery and two markers of long-term renal impairment that were differentially expressed between groups (1.2-2.6 fold-change, p<0.05). Differentially expressed proteins were enriched in pro-inflammatory signaling pathways: Glycoprotein VI (activated during ADHF development, adjusted p<0.01) and acute phase response (repressed during recovery from ADHF, p<0.01). This research identified 20 candidate protein markers of kidney injury, including 6 promising candidates supported by existing evidence and 14 novel candidates never implicated in AKI. Early awareness of AKI in ADHF through the use of biomarkers has the potential to reduce mortality and improve outcomes for these at-risk patients.
2022-01-19 | PXD028983 | Pride
Project description:MicroRNA sequencing of myocardium of ovine comparing normal (Control), paced-induced heart failure (HF) and heart failure recovery (HF-R) after discontinuation of pacing.
2017-09-15 | GSE87468 | GEO
Project description:MicroRNA profiling of myocardium of ovine comparing normal (Control), paced-induced heart failure (HF) and heart failure recovery (HF-R) after discontinuation of pacing.
2017-09-15 | GSE87449 | GEO
Project description:IntroductionAcute kidney disease (AKD) represents a continuum of kidney injury for 7 to 90 days after acute kidney injury (AKI). The incidence and prognosis of AKD after acute decompensated heart failure (ADHF) are currently unclear. The aims of this study were to explore the incidence of AKD and the transition from AKI to AKD, to identify risk factors for AKD and develop a prediction model for any-stage AKD, and to evaluate the prognosis of AKD.MethodsA total of 7519 patients admitted for ADHF between January 1, 2008, and December 31, 2018, from a multi-institutional database were identified. The composite outcomes after ADHF were stage 3 AKD and all-cause death. The prognosis impact of AKD, including major adverse kidney events (MAKEs), all-cause death, and heart failure hospitalization (HFH), during 5 years of follow-up was analyzed.ResultsThe overall incidence of AKI and AKD after ADHF was 9% and 21.2%, respectively; 39.4% of the patients diagnosed with having AKI during ADHF subsequently developed AKD whereas 19.4% of the patients without an identified AKI episode subsequently developed AKD. The predictive scoring models revealed C-statistics of 0.726 (95% CI: 0.712-0.740) for any-stage AKD and 0.807 (95% CI: 0.793-0.821) for the composite of stage 3 AKD and death. Finally, AKD was associated with higher risks of all-cause death, MAKE, and HFH during the 5 years of follow-up (P < 0.001).ConclusionAKD after ADHF are associated with adverse outcomes. Our model could help in identification of patients at risk for AKD development, especially in those who did not have an index AKI episode.
| S-EPMC8897687 | biostudies-literature
Project description:BACKGROUND Acute decompensated heart failure (ADHF) is associated with deterioration in renal function-an important risk factor for poor outcomes. Whether ADHF results in permanent kidney damage/dysfunction is unknown. METHODS AND RESULTS We investigated for the first time the renal responses to the development of, and recovery from, ADHF using an ovine model. ADHF development induced pronounced hemodynamic changes, neurohormonal activation, and decline in renal function, including decreased urine, sodium and urea excretion, and creatinine clearance. Following ADHF recovery (25 days), creatinine clearance reductions persisted. Kidney biopsies taken during ADHF and following recovery showed widespread mesangial cell prominence, early mild acute tubular injury, and medullary/interstitial fibrosis. Renal transcriptomes identified altered expression of 270 genes following ADHF development and 631 genes following recovery. A total of 47 genes remained altered post-recovery. Pathway analysis suggested gene expression changes, driven by a network of inflammatory cytokines centered on IL-1β (interleukin 1β), lead to repression of reno-protective eNOS (endothelial nitric oxide synthase) signaling during ADHF development, and following recovery, activation of glomerulosclerosis and reno-protective pathways and repression of proinflammatory/fibrotic pathways. A total of 31 dysregulated genes encoding proteins detectable in urine, serum, and plasma identified potential candidate markers for kidney repair (including CNGA3 [cyclic nucleotide gated channel subunit alpha 3] and OIT3 [oncoprotein induced transcript 3]) or long-term renal impairment in ADHF (including ACTG2 [actin gamma 2, smooth muscle] and ANGPTL4 [angiopoietin like 4]). CONCLUSIONS In an ovine model, we provide the first direct evidence that an episode of ADHF leads to an immediate decline in kidney function that failed to fully resolve after ≈4 weeks and is associated with persistent functional/structural kidney injury. We identified molecular pathways underlying kidney injury and repair in ADHF and highlighted 31 novel candidate biomarkers for acute kidney injury in this setting.
| S-EPMC8649508 | biostudies-literature
Project description:Transcriptomic responses of the kidney to development of and recovery from acute decompensated heart failure (ADHF)
| PRJNA748425 | ENA
Project description:Canine tachycardia-induced cardiomyopathy caused by several weeks of rapid ventricular pacing is a well-established animal model of congestive heart failure. However, little is known about the underlying changes in gene expression that occur in the canine myocardium after the induction of heart failure. This project aims to compare expression profiles in left ventricular free wall samples from control dogs and dogs with pacing-induced heart failure on the custom MuscleChip. Keywords: other
2003-07-16 | GSE472 | GEO
Project description:BackgroundAcute kidney injury (AKI) in the context of acute decompensated heart failure (ADHF) encompasses a broad spectrum of phenotypes with associated disparate outcomes. We evaluate the impact of 'ongoing AKI' on prognosis and cardiorenal outcomes and describe predictors of 'ongoing AKI'.MethodsA prospective multicentre observational study of patients admitted with ADHF requiring intravenous furosemide was completed, with urinary angiotensinogen (uAGT) measured at baseline. AKI was defined using Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria. AKI recovery status was defined as 'no AKI', 'recovered AKI' or 'ongoing AKI' based on renal function at hospital discharge. Event-free survival analysis was performed to predict death and cardiorenal outcomes at hospital discharge and 6-month follow-up. Multinomial logistic regression was performed to identify predictors of ongoing AKI. Multiclass receiver operator curve analysis was performed to evaluate the relationship between renin-angiotensin system (RAS) blockers and uAGT in predicting ongoing AKI.ResultsAmong 271 enrolled patients, 121 (44.6%) patients developed AKI, of whom 62 patients had ongoing AKI. Ongoing AKI was associated with increased risk of death (HR 6.89, p<0.001), in-hospital end-stage kidney disease (HR 44.39, p<0.001), 6-month composite of death, transplant, left ventricular assist device and heart failure hospitalisation (HR 3.09, p<0.001), and 6-month composite major adverse kidney events (HR 5.71, p<0.001). Elevated baseline uAGT levels, chronic beta-blocker and thiazide diuretic therapy, and lack of RAS blocker prescription at recruitment were associated with ongoing AKI. While uAGT levels were lower with RAS blocker prescription, in patients with ongoing AKI, uAGT levels were elevated regardless of RAS blocker status.ConclusionPatients experiencing ongoing AKI during ADHF admission were at increased risk of death and other adverse cardiorenal outcomes. Differential uAGT response in patients receiving RAS blockers with ongoing AKI suggests biomarkers may be helpful in predicting treatment responses and cardiorenal outcomes.
| S-EPMC11751981 | biostudies-literature
Project description:Heart disease is a common cause of morbidity and mortality during pregnancy. Symptoms and signs of heart failure in a pregnant woman are an indication for urgent assessment to establish a diagnosis and appropriate management. This is best accomplished through a multidisciplinary approach in which both cardiologists and obstetricians need to participate in order to provide expert counselling and care in pursuit of safe motherhood. Congenital heart disease, although common, once corrected is an unusual source of complications, which are more likely to develop as a consequence of ventricular failure, pulmonary hypertension and aortic arch disease. Rheumatic valvular heart disease is a challenge because of the need for anticoagulation during pregnancy and the risk of sepsis associated with childbirth. This review outlines a contemporary approach to heart failure presenting during pregnancy.
| S-EPMC5491013 | biostudies-other
Project description:Recovery of cardiac function is the ultimate goal of heart failure therapy yet is infrequently observed and remains poorly understood. Here we characterize the cellular landscape and predictors of cardiac recovery by performing single nucleus RNA-sequencing (snRNA-seq) from 40 heart failure patients who recovered LV systolic function following left ventricular assist device (LVAD) implantation and patients who did not recover and non-diseased donors. We identify cell type specific transcriptional signatures of recovery in all cell types, most prominently in macrophages and fibroblasts. Pro-inflammatory macrophages and inflammatory signalling in fibroblasts were negative predictors of recovery, while downregulation of RUNX1 transcriptional activity in macrophages and fibroblasts was associated with recovery. In silico perturbation of RUNX1 in macrophages and fibroblasts recapitulated the transcriptional state of recovery. In a mouse model of cardiac recovery mediated by BRD4 inhibition, we observed a decrease in macrophage and fibroblast Runx1 expression, diminished chromatin accessibility within a Runx1 intronic peak, and acquisition of human recovery signatures. These findings suggest that cardiac recovery is a unique biological state and identify RUNX1 as a possible therapeutic target to facilitate cardiac recovery.
2023-02-28 | GSE226314 | GEO