Abstract

Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies.

Highlights

  • Systems biology is a term selected for the study of the vast amount of experimental data advanced from current technologies in genomics and proteomics [1]

  • The specific clinical models developed to interpret the variety of clinical phenotypes are not sufficiently coherent to explain the progressive deterioration of heart failure and some of the successful aspects of the new therapeutic agents

  • It is accepted that early mechanical stresses applied in the myocytes and/or mechanical changes in the left ventricular cavity comprise the primary initiating causes for cardiac remodeling and neurohormonal activation

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Summary

Introduction

Systems biology is a term selected for the study of the vast amount of experimental data advanced from current technologies in genomics and proteomics [1]. It is accepted that early (initial) mechanical stresses applied in the myocytes and/or mechanical changes in the left ventricular cavity comprise the primary initiating causes for cardiac remodeling and neurohormonal activation. The methodology of systems biology defines the early mechanical stresses, the clinical functional modules and the clinical phenotypes of the heart failure syndrome.

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