Project description:Molecular analysis of the effect left ventricular assist device (LVAD) support has on congestive heart failure patients. Keywords = Congestive heart failure, left ventricular assist device, eNOS, gene, dimethylarginine dimethylaminohydrolase Keywords: other
Project description:To provide comprehensive characterization of the cardiac proteome of advanced human heart failure, we performed mass spectrometry-based label free proteomic analysis of left ventricular samples obtained from 149 human heart failure patients and 9 non-failing controls. All heart failure biopsy samples were collected at the time of heart transplantation or assist device implantation. To characterize signaling perturbations, we performed phosphoproteomic analysis for 32 representative heart failure samples and 8 non-failing controls.
Project description:19 paired human left ventricular apex samples were harvested at the time of implant of a left ventricular assist device (PRE) and at the time of explant (POST). The cohort included patients that were clinically classified as ischemic (I) showing evidence of coronary artery disease, non-ischemic (N) no evidence of coronary artery disease or acute Myocardial infarction (IM) myocardial infarction within 10 days of the implant. Tissue was processed and hybridized to the Affymetrix HG-U133A chip.
Project description:19 paired human left ventricular apex samples were harvested at the time of implant of a left ventricular assist device (PRE) and at the time of explant (POST). The cohort included patients that were clinically classified as "ischemic" (I) showing evidence of coronary artery disease, "non-ischemic" (N) no evidence of coronary artery disease or "acute Myocardial infarction" (IM) myocardial infarction within 10 days of the implant. Tissue was processed and hybridized to the Affymetrix HG-U133A chip. Keywords: other
Project description:In this study, we performed single-nuclei RNA sequencing on heart samples from 6 end-stage heart failure patients (3 ischemic cardiomyopathy and 3 non-ischemic cardiomyopathy). Each of these patients was treated with a left ventricular assist device (LVAD). Analysis of the longitudinal effect of LVAD at the transcriptomic level revealed a common signature profile related to the glucocorticoid receptor, independent of etiologies. Specifically, four genes promoting cardiac fatty acid metabolism, repair, and anti-inflammatory action were highlighted: FKBP5, ZBTB16, FOXO3, and PDK4.
Project description:Exploratory Study on the Mechanism of Left Ventricular Function Recovery After Left Ventricular Assist Device Implantation in Pediatric Dilated Cardiomyopathy
Project description:Heart failure is associated with high morbidity and mortality and its incidence increases worldwide. MicroRNAs (miRNAs) are potential markers and targets for diagnostic and therapeutic applications, respectively. We determined myocardial and circulating miRNA abundance and its changes in patients with stable and end-stage heart failure before and at different time points after mechanical unloading by a left ventricular assist device (LVAD) by small-RNA-sequencing. MiRNA changes in failing heart tissues partially resembled that of fetal myocardium. Consistent with prototypical miRNA–target-mRNA interactions, target mRNA levels were negatively correlated to changes in abundance for highly expressed miRNAs in heart failure and fetal hearts. The circulating small RNA profile was dominated by miRNAs, and fragments of tRNAs and small cytoplasmic RNAs. Heart- and muscle-specific circulating miRNAs (myomirs) increased up to 140-fold in advanced heart failure, which coincided with a similar increase in cardiac troponin I protein, the established marker for heart injury. These extracellular changes nearly completely reversed 3 months following initiation of LVAD support. In stable heart failure, circulating miRNAs showed less than 5-fold differences compared to normal, and myomir and cardiac troponin I levels were only captured near the detection limit. These findings provide the underpinning for miRNA-based therapies and emphasize the usefulness of circulating miRNAs as biomarkers for heart injury performing similar to established diagnostic protein biomarkers. Total RNA isolated from human left ventricular myocardium of failing hearts due to dilated or ischemic cardiomyopathy before and after mechanical unloading by a left ventricular assist device (LVAD), and fetal myocardium compared to non-failing postnatal myocardium.
Project description:Heart failure is a leading cause of death worldwide, and patients with severe heart failure require left ventricular assist device (LVAD) support. LVAD is usually implanted as a bridge to transplantation (BTT) or destination but can be removed if the patient’s cardiac function recovers. We performed liquid chromatography–mass spectrometry on myocardial samples from heart transplant recipientHowever to identify the molecular predictors for cardiac prognosis after LVAD implantation. Ref: Shintani-Domoto Y, Ode KL, Nomura S et al. Circulation 152, 1518-1521 (2025)
