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: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: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 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 miRNAM-bM-^@M-^Starget-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, and fetal myocardium compared to non-failing postnatal myocardium was subjected to multiplexed small RNA-sequencing on the Illumina platform. mRNA gene expression data using Illumina HumanHT-12v4 beadarrays for a subset of the myocardial samples is available (GSE52601).
Project description:Continuous-flow left ventricular assist devices commonly lead to aortic regurgitation, which results in decreased pump efficiency and worsening heart failure. We hypothesized that non-physiological wall shear stress and oscillatory shear index alter the abundance of structural proteins in aortic valves of left ventricular assist device (LVAD) patients. Doppler images of aortic valves of patients undergoing heart transplants were obtained. Eight patients had been supported with LVADs, whereas 10 were not. Aortic valve tissue was collected and protein levels were analyzed using mass spectrometry. Echocardiographic images were analyzed and wall shear stress and oscillatory shear index were calculated. The relationship between normalized levels of individual proteins and in vivo echocardiographic measurements was evaluated. Of the 57 proteins of interest, there was a strong negative correlation between levels of 15 proteins and the wall shear stress (R < -0.500, p ? 0.05), and a moderate negative correlation between 16 proteins and wall shear stress (R ?0.500 to ?0.300, p ? 0.05). Gene ontology analysis demonstrated clusters of proteins involved in cellular structure. Proteins negatively correlated with WSS included those with cytoskeletal, actin/myosin, cell-cell junction and extracellular functions. In aortic valve tissue, 31 proteins were identified involved in cellular structure and extracellular junctions with a negative correlation between their levels and wall shear stress. These findings suggest an association between the forces acting on the aortic valve (AV) and leaflet protein abundance, and may form a mechanical basis for the increased risk of aortic leaflet degeneration in LVAD patients.
Project description:This study investigated factors associated with left ventricular (LV) recovery in pediatric dilated cardiomyopathy (DCM) following left ventricular assist device (LVAD) implantation, using single-cell multiomics analysis. Twenty-five pediatric DCM patients who underwent bridge-to-transplant LVAD (BTT-LVAD) implantation at our institution were categorized as either recovery (R) cases, defined by successful LVAD explantation with sustained stability on medical therapy, or non-recovery (NR) cases, defined by the need for transplantation or death. Single-nucleus RNA (snRNA) sequencing and chromatin accessibility analyses were conducted on six subcases (three from each group). Candidate genes and pathways identified were further validated through histological and serological assessments in all cases. Pseudobulk analysis revealed higher expression of NPPB, MYL7, and PCDH9 in cardiomyocytes from the R group, with NPPB exhibiting the highest baseline expression and corresponding changes in chromatin accessibility. Gene Ontology analysis highlighted pathways regulating apoptosis. Serum BNP, a protein product of NPPB, was significantly elevated in the R group at the time of LVAD implantation and correlated with a higher proportion of non-apoptotic cells.