Dynamic adaptation of myocardial proteome during heart failure development

Abstract

Heart failure (HF) development is characterized by huge structural changes that are crucial for disease progression. Analysis of time dependent global proteomic adaptations during HF progression offers the potential to gain deeper insights in the disease development and identify new biomarker candidates. Therefore, hearts of TAC (transverse aortic constriction) and sham mice were examined by cardiac MRI on either day 4, 14, 21, 28, 42, and 56 after surgery (n = 6 per group/time point). At each time point, proteomes of the left (LV) and right ventricles (RV) of TAC and sham mice were analyzed by mass spectrometry (MS). In TAC mice, systolic LV heart function worsened from day 4 to day 14, remained on a stable level from day 14 to day 42, and showed a further pronounced decline at day 56. MS analysis identified in the LV 330 and in RV 246 proteins with altered abundance over time (TAC vs. sham, fc≥±2). Functional categorization of proteins disclosed the time-dependent alteration of different pathways. Heat shock protein beta-7 (HSPB7) displayed differences in abundance in tissue and serum at an early stage of HF. This study not only provides an overview of the time dependent molecular alterations during transition to HF, but also identified HSPB7 as a novel blood biomarker candidate for the onset of cardiac remodeling.

Identification of Fat Storage-Inducing Transmembrane Proteins 1 and 2 as Putative Therapeutic Targets for Heart Failure by Integrated Analysis of Proteome and Transcriptome

“…In the transcriptome analysis, the genes up-regulated in heart failure included ANP and BNP, well known up-regulated proteins in heart failure. In addition, about 10% genes showed the changes of expression level, which is consistent to that relatively small number of proteins were regulated in TAC mice [42]. Collectively, our transcriptome dataset also suggested to be the good quality.…”

circSnx12 Is Involved in Ferroptosis During Heart Failure by Targeting miR-224-5p

“…MiRNA dataset (GSE99459) was downloaded from GEO, and the corresponding platform annotation information were also retrieved to convert the probe information into the corresponding gene name. Rudebusch et al ( 20 ) obtained the protein expression profiles of HF through mass spectrometry (MS), and the raw date are available via ProteomeXchange with identifier PXD007171. Werfel et al ( 21 ) obtained the circRNA expression data of HF through deep sequencing techniques and the raw date were published on PUBMED with identifier PMID27476877 ( Table 1 ).…”

“…“Limma” package in R software was used to identify the differentially expressed miRNAs with thresholds of |logFC|>1 and P < 0.05. Both mRNA and circRNA data were extracted from the research results of Rudebusch et al ( 20 ) and Werfel et al ( 21 ), respectively, which had been uploaded to PUBMED.…”

HSPB7 regulates osteogenic differentiation of human adipose derived stem cells via ERK signaling pathway

“…Heat shock protein B7 ( HSPB7 ), also known as cardiovascular heat shock protein (cvHsp), belongs to the small heat shock protein family with essential roles in maintaining cellular homeostasis in a variety of both physiological and pathophysiological processes [ 13 – 15 ]. HSPB7 is highly expressed in the cardiac tissue and plays a critical role in cardiac metabolism [ 16 ]. The dysfunction of HSPB7 is strongly associated with heart failure, dilated cardiomyopathy, and idiopathic cardiomyopathy [ 17 ].…”