Interatrial differences of basal molecular set‐up and changes in tachycardia‐induced heart failure–a proteomic profiling study

Abstract

AimsLeft and right atria show compelling differences regarding organogenesis and specific clinical diseases. In congestive heart failure (CHF), remodelling of the atria occurs leading to increased arrhythmogenic susceptibility and deterioration of clinical symptoms. We aimed to assess the basal left and right atrial molecular set-up and different chamber-specific atrial changes in heart failure. Methods and resultsWe combined an animal model of rapid ventricular pacing induced heart failure in the rabbit and a gel-based proteomic screening of left and right atrial specimen. A gene ontology over-representation analysis was performed for biological function. Ultrastructural adaptations were evaluated using transmission electron microscopy. Comparing left and right atria of healthy control animals (CTRL), 39 proteins displayed significant expression differences involving various biological functions. Upon further statistical analyses, four pathways of energy metabolism were confirmed to be significantly over-represented beneath the other biological processes. Rapid ventricular pacing induced severe left ventricular systolic dysfunction, symptomatic heart failure and a macroscopic atrial remodelling. In CHF versus CTRL, metabolic and antioxidative enzymes were differentially expressed and showed chamber-specific bidirectional alterations. Transmission electron microscopy visualized a remarkable and again chamber-specific ultrastructural disturbance of mitochondrial morphology.

Combined Inhibition of the Renin-Angiotensin System and Neprilysin Positively Influences Complex Mitochondrial Adaptations in Progressive Experimental Heart Failure

“…This was also confirmed by our work group when evaluating proteomic alterations in left ventricles [17] and atria [18]. But despite recognition of its importance, mitochondrial adaptations remain nevertheless insufficiently characterized during progression to overt heart failure and therefore deserve further evaluation to potentially identify new therapeutic targets.…”

“…Six untreated animals served as controls (CTRL). ELVD and CHF was induced by a standardized protocol of progressive rapid right ventricular pacing as described previously [17,19,20,15,18]. In brief, animals of the ELVD group were paced with 330 beats per minute (bpm) for 10 days, and animals of the CHF group underwent an additional pacing period at 360 bpm for further 10 days.…”

The German AugUR study: study protocol of a prospective study to investigate chronic diseases in the elderly

“…The short echocardiographic program focuses on left ventricular function and the morphology of the four heart chambers accounting for chamber-specific cardiac remodeling processes [ 23 ]. Cardiac morphology including areas and volumes of the four heart chambers determined in the apical four- and two-chamber views as well as left ventricular dimensions assessed by two-dimensional guided M-mode in the left parasternal long axis view are recorded [ 24 ].…”

NT-proBNP Predicts Cardiovascular Death in the General Population Independent of Left Ventricular Mass and Function: Insights from a Large Population-Based Study with Long-Term Follow-Up

“…In the case of any direct association of BNP on mortality independent of cardiac remodelling, at least a part of the association of BNP (or NT-proBNP) with mortality should be independent of measures of cardiac remodelling. In published literature, cardiac remodelling processes [ 10 , 11 ] are complex, interrelated and chamber-specific at the molecular and cellular level. These complex processes manifest clinically.…”