Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors.

Heart Failure in Patients with Preserved Ejection Fraction: Questions Concerning Clinical Progression.

Over the last two decades, important advances have been made in explaining some pathophysiological aspects of heart failure with preserved ejection fraction (HFpEF) with repercussions for the successful clinical management of the syndrome. Despite these gains, our knowledge for the natural history of clinical progression from the pre-clinical diastolic dysfunction (PDD) until the final clinical stages is significantly limited. The subclinical progression of PDD to the clinical phenotype of HFpEF and the further clinical progression to some more complex clinical models with multi-organ involvement, similar to heart failure with reduced ejection fraction (HFrEF), continue to be poorly understood.

Heart failure: a complex clinical process interpreted by systems biology approach and network medicine.

Systems biology is founded on the principles of integrative computational analysis and on the data from genetic and molecular components. The integration of biological components produces interacting networks, modules and phenotypes with remarkable applications in the field of clinical medicine. The evolving concept of network medicine gives a more precise picture of the intrinsic complexity of failing myocardium and its clinical consequences.

Systems biology and biomechanical model of heart failure.

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.

A conceptual paradigm of heart failure and systems biology approach.

Purpose Of Review: The understanding of heart failure syndrome is increased and the interpretation of the related underlying mechanisms is improved by the integrated molecular, network and phenotype analyses of systems biology methodology. Heart failure can be explained as a complex, unstable, adaptive and self-organized biological phenomenon with intrinsic regulatory mechanisms.

Recent Findings: The systems biology approach, that synthesizes information from biological molecules and networks involved in heart failure progression, leads from the regulatory modules of natriuretic peptide system and RAAS, to a more comprehensive network-based biological system with clinical significance.