Interacting Network Analysis and Functional Profiling to Look Inside Adverse Ventricular Remodeling Post- Myocardial Infarction

Dysfunction of the left ventricle occurs to a varying degree in the most of surviving patients' post-myocardial infarction. In these patients, adverse remodeling frequently culminates in heart failure. Being able to predict patients who will progress to congestive heart failure would greatly advance in clinical prognostic capabilities. The aim of this study was two-fold: to improve the knowledge on functional pathways of early and late left ventricleremodeling processes, and to generate new hypotheses to identify putative prognostic indicators for heart failure. To this purpose, we carried out a systems biology study using protein lists previously identified by proteomic studies. Twenty-seven journal articles were included in our analysis. We generated two protein lists:a list of circulating proteins associated with adverse left ventricleremodeling (early changes); anda list of proteins found differentially expressed in ventricle tissue of patients with heart failure (later phase). We separately analyzed the protein sets by a combination of pioneering bioinformatics portals available on web. We obtained significant enrichments of blood proteins involved in extracellular matrix remodeling, collagen catabolism, response to stress, and the inflammatory response, while the alterations in the left ventricle reflected remarkable activation of the respiratory chain coupled with ATP production and oxidative metabolism. We provided new insights into the pathogenesis of adverse ventricularremodeling and heart failure and we brought to light some intermediate proteins likely involved in the disease mechanisms not previously associated with the failing status, supplying a new rationale for drug development and further discovery of biomarkers of these heart pathologies.