Dataset Information

Analysis of Left Ventricular Profiles in Carfilzomib Treated and Control Mouse Specimens

ABSTRACT: Wild-type C57BL/6N mice were treated with twice-weekly carfilzomib injections for a period of two weeks. Following this treatment, the left ventricular tissues were prepared for tmt-multiplexed mass spectrometry analysis to determine the protein-profiles of the treated hearts as opposed to those of untreated mouse specimens. For more experimental details and procedures, please see the attached methods file.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Dr. Edward Lau

PROVIDER: PXD046670 | JPOST Repository | Wed Nov 08 00:00:00 GMT 2023

REPOSITORIES: jPOST

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			Action	DRS
	20230916_COH_CFZ_Mouse_Heart_TMT_F14.mzML	Mzml
	20230916_COH_CFZ_Mouse_Heart_TMT_F14.raw	Raw
	20230916_COH_CFZ_Mouse_Heart_TMT_F17.mzML	Mzml
	20230916_COH_CFZ_Mouse_Heart_TMT_F17.raw	Raw
	20230916_COH_CFZ_Mouse_Heart_TMT_F18.mzML	Mzml

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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).

Dataset Information

Analysis of Left Ventricular Profiles in Carfilzomib Treated and Control Mouse Specimens

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