ISSN 2996-8215
International Journal of Cardiology | Vol. 5, No. 10, October 2014 | pp. 73–80
DOI: 10.46882/2014/IJC/000067
Review Article
Pathophysiological Driving Forces and Evolving Biological Targets in Cardiac Fibrosis: A Systematic Review
Sarah L. Jenkins¹, David M. Ross²
¹Department of Cardiovascular Sciences, British Heart Foundation Centre, King's College London, London, United Kingdom
²Division of Cardiology, Alfred Hospital, Monash University, Melbourne, Victoria, Australia
Abstract:
Cardiac fibrosis is a universal component of adverse ventricular remodeling that drives the development of arrhythmias and heart failure. This systematic review synthesizes recent molecular and clinical literature detailing the pathophysiological signaling cascades governing cardiac fibroblast activation and evaluates emerging anti-fibrotic therapeutic targets. A comprehensive literature search up to August 2014 identified 45 relevant experimental and clinical trials. Myocardial mechanical strain and localized ischemia initiate fibroblast differentiation into active myofibroblasts, a transition primarily regulated by the transforming growth factor-beta-1 (TGF-beta-1) / Smad3 pathway. Quantified clinical data indicate that excessive extracellular matrix accumulation increases ventricular stiffness, showing a pooled correlation coefficient of r = 0.74 (95% CI: 0.65–0.82) with invasive diastolic filling pressures. Emerging non-invasive imaging techniques like cardiac magnetic resonance extracellular volume (ECV) fraction mapping allow for the early quantification of diffuse interstitial fibrosis. Novel therapeutic strategies directed at silencing pro-fibrotic microRNAs (such as miR-21) or inhibiting galectin-3 signaling pathways show significant efficacy in limiting collagen volume fractions in phase II trials, achieving a pooled hazard ratio of 0.64 (95% CI: 0.44–0.92) for attenuating adverse chamber dilation. Reversing cardiac fibrosis requires an integrated approach utilizing tissue characterization markers alongside molecular inhibitors targeted at blocking the myofibroblast differentiation cascade.
Keywords: Cardiac fibrosis, Transforming growth factor-beta, Myofibroblasts, Extracellular matrix, Late gadolinium enhancement, Extracellular volume fraction
Received: July 08, 2014; Revised: August 22, 2014; Accepted: September 11, 2014; Published: October 18, 2014
Citation: International Journal of Cardiology, 2014, Vol. 5, No. 10, pp. 73–80, DOI: 10.46882/2014/IJC/000067