The effect of disease on human cardiac protein expression profiles in paired samples from right and left ventricles

Abstract

BackgroundCardiac diseases (e.g. coronary and valve) are associated with ventricular cellular remodeling. However, ventricular biopsies from left and right ventricles from patients with different pathologies are rare and thus little is known about disease-induced cellular remodeling in both sides of the heart and between different diseases. We hypothesized that the protein expression profiles between right and left ventricles of patients with aortic valve stenosis (AVS) and patients with coronary artery disease (CAD) are different and that the protein profile is different between the two diseases. Left and right ventricular biopsies were collected from patients with either CAD or AVS. The biopsies were processed for proteomic analysis using isobaric tandem mass tagging and analyzed by reverse phase nano-LC-MS/MS. Western blot for selected proteins showed strong correlation with proteomic analysis.ResultsProteomic analysis between ventricles of the same disease (intra-disease) and between ventricles of different diseases (inter-disease) identified more than 500 proteins detected in all relevant ventricular biopsies. Comparison between ventricles and disease state was focused on proteins with relatively high fold (±1.2 fold difference) and significant (P < 0.05) differences. Intra-disease protein expression differences between left and right ventricles were largely structural for AVS patients and largely signaling/metabolism for CAD. Proteins commonly associated with hypertrophy were also different in the AVS group but with lower fold difference. Inter-disease differences between left ventricles of AVS and CAD were detected in 9 proteins. However, inter-disease differences between the right ventricles of CAD and AVS patients were associated with differences in 73 proteins. The majority of proteins which had a significant difference in one ventricle compared to the other pathology also had a similar trend in the adjacent ventricle.ConclusionsThis work demonstrates for the first time that left and right ventricles have a different proteome and that the difference is dependent on the type of disease. Inter-disease differential expression was more prominent for right ventricles. The finding that a protein change in one ventricle was often associated with a similar trend in the adjacent ventricle for a large number of proteins suggests cross-talk proteome remodeling between adjacent ventricles.

Remote ischaemic preconditioning in isolated aortic valve and coronary artery bypass surgery: a randomized trial†

“…Coronary artery and aortic valve disease are associated with specific disease-induced cellular remodeling, since they may exhibit specific cellular proteome and may response differently to ischemic reperfusion injury 9 . Similarly, left and right ventricle may have, as previously demonstrated, different protein profile 9 . Different Authors 10-12 , upon calculating markers of ischemic stress including phosphorylation potential and energy charge, found RIPC to have significant effect.…”

Monoamine Oxidase Is Overactivated in Left and Right Ventricles from Ischemic Hearts: An Intriguing Therapeutic Target

“…Therefore, despite a qualitative similarity of the biochemical mechanisms, generating oxygen and carbonyl reactive species (i.e., MAO activity), the elicited scavenging response was quantitatively different in the RV and LV, suggesting that RV might be less equipped than LV to counter oxidative/carbonyl stress. Accordingly, Littlejohns et al [45] showed a more prominent change of protein expression profiles in the diseased RV compared to LV. Lipid peroxidation and protein carbonylation are likely to result from severe oxidative stress contributing to dysfunction of heart contractility [46].…”

Dysregulation of Mesenchymal Stromal Cell Antioxidant Responses in Progressive Multiple Sclerosis

“…Liquid chromatography‐tandem mass spectrometry (LC‐MSMS) of C‐MSC and MS‐MSC conditioned medium was performed by the University of Bristol Proteomics Facility using a previously described protocol for tandem mass tagging (Thermo Fisher Scientific USA) coupled to liquid chromatography‐mass spectrometry . Values were normalized to a randomly selected control.…”

“…The supernatant was collected and stored at −80 C. Protein content was determined using the Qubit Fluorometer and Quant-iT Protein assay kit (Invitrogen USA) according to manufacturer's instructions and diluted to 2 mg/ml. Liquid chromatography-tandem mass spectrometry (LC-MSMS) of C-MSC and MS-MSC conditioned medium was performed by the University of Bristol Proteomics Facility using a previously described protocol for tandem mass tagging (Thermo Fisher Scientific USA) coupled to liquid chromatography-mass spectrometry [31]. Values were normalized to a randomly selected control.…”