Cardiac fibrosis in heart failure

The prevalence of Heart Failure (HF) is approximately 1-2% in adult population, rising to more than 10% of elderlies over 70 years of age 1 2. Epidemiological studies show high incidence and prevalence of HF among elderlies. The prognosis of HF in this population is poor with rising cases of hospitalization, comorbidity and health costs 3-5. Cardiac remodeling is a cardinal process mediating the progression to HF. Cardiac fibroblasts (CFs) play a critical role in the regulation of left ventricular remodeling following myocardial infarction 6 7, mainly through the excessive extracellular matrix (ECM) protein deposition and their differentiation to a myofibroblast phenotype 8 with excessive proliferatory and migratory properties. This process known as cardiac fibrosis is crucial for the structural integrity of the myocardial tissue. However in the advanced phases, cardiac fibrosis leads to ventricular stiffness, altered chamber compliance and contractile dysfunction, in addition cardiac fibrosis impairs the electrical coupling of cardiomycytes increasing the risk of developing potential arrythmias and fatal events 9-11. Heart tissue is constituted by cardiomyocytes, CFs, endothelial and neuronal cells. Initially it was thought that CFs are the most prevalent cell type accounting for up to 70% of cells 12, recent studies report that the CFs population is not more than 20% of whole cell population in murine cardiac tissue 13. Although the numerous CFs markers reported in the present literature, like vimentin, alpha-smooth muscle actin, collagen 1 alpha1, periostin, discoidin domain receptor-2, fibroblast specific protein-1, thymus cell antigen-1, the transcription factor 21, platelet derived growth factor receptoralpha 14, a robust specific molecular biomarker of both resident and activated CFs is still lacking. The absence of a universal marker for the detection of CFs can be the explanation to the different interpretation of results on CFs cell number reported till now. The prevalence of heart failure is rising with poor prognosis and health costs. Cardiac remodeling is a cardinal process mediating the progression to heart failure, and cardiac fibroblasts play a critical role in the regulation of left ventricular remodeling mainly through the excessive extracellular matrix protein deposition and their differentiation to a myofibroblast phenotype with excessive proliferative and migratory properties. All this characteristics are known also as cardiac fibrosis. This process is crucial for the structural integrity of myocardial tissue. After myocardial infarction, are activated two important type of cardiac fibrosis: reparative and reactive cardiac fibrosis. Both of them are mediated by a huge number of inflammatory and hormonal mediators. In this review we will focus on the role of three important systems involved in cardiac fibrosis and described as the great contributors in heart failure: inflammatory, RAA and beta-adrenergic system. The deeper understanding of these great contributors is of interest in the development of new therapeutic strategies toward cardiac fibrosis and heart failure.