Proteomic profiling of non-ischemic myocardium following acute mechanical cardiac unloading in ischemic heart failure

Background The cardiac proteome responds to various physiological and pathological stimuli. While acute left ventricle (LV) unloading by catheter-based LV assist device is now a therapeutic option for heart failure, its impact on cardiac proteins is unknown. We sought to characterize proteomic remodeling associated with altered LV load in ischemic heart failure. Methods Sixteen Yorkshire pigs underwent myocardial infarction (MI) and were subjected one week later to either 2-hour acute mechanical LV unloading ( n = 6), 2-hour LV overloading with mechanically-induced acute aortic regurgitation ( n = 4), or no load interventions ( n = 6). Non-ischemic remote myocardium was processed for proteomics. Age-matched naïve pigs ( n = 6) served as reference. Protein abundance was analyzed using four-group LIMMA moderated ANOVA and pairwise LIMMA moderated t -tests. These were followed by functional enrichment and STRING functional association network analysis of ANOVA-significant proteins together with exploratory screening for load-associated candidates. Results A total of 1713 proteins were identified, of which 1552 were included in the statistical analysis, and 7 remained significant after multiple-testing correction. Pairwise analyses revealed that significant protein-level differences were predominantly observed between the MI and Sham groups, whereas protein changes in response to 2-h of acutely altered LV load were limited. An exploratory screening identified six load-associated candidate proteins, with ITIH1 and MYOZ2 selected as representative candidates. Independent human transcriptomic analysis suggested disease-related context of these candidates. Conclusions Proteomic remodeling of the non-ischemic remote myocardium in response to acutely altered LV load was less prominent compared to the impact of MI. Exploratory analysis identified LV load-associated candidate proteins.