The Living Scar – Cardiac Fibroblasts and the Injured Heart

Cardiac scars, often dubbed ‘dead tissue’, are very much alive, with heterocellular activity contributing to the maintenance of structural and mechanical integrity following heart injury. To form a scar, non-myocytes such as fibroblasts are recruited from intra- and extra-cardiac sources. Fibroblasts perform important autocrine and paracrine signaling functions. They also establish mechanical and, as is increasingly evident, electrical junctions with other cells. While fibroblasts were previously thought to act simply as electrical insulators, they may be electrically connected among themselves and, under some circumstances, to other cells including cardiomyocytes. A better understanding of these biophysical interactions will help to target scar structure and function, and will facilitate the development of novel therapies aimed at modifying scar properties for patient benefit.

TrendsCardiac scars caused by injury are often considered to be inert tissue serving predominantly structural roles and representing obstacles to electrical impulse conduction in the heart. This view is currently changing.Cardiac fibroblasts, a highly heterogeneous population of electrically non-excitable cells of diverse origins, form hubs of classic biochemical (autocrine, paracrine) and biophysical signaling. The latter includes homo- and heterocellular mechanical and electrical coupling.The extent, regulation, and relevance – in particular of heterocellular biophysical interactions of different cell types with cardiac fibroblasts – remain elusive and represent highly relevant translational research targets.An understanding of these interactions may hold the key to unlocking a conceptually novel approach to cardiac therapy: helping the heart to form ‘better scars’.This review explores available insight and recent concepts on fibroblast integration in the heart, and highlights potential avenues for harnessing their roles to optimize scar function following heart injury such as infarction, and therapeutic interventions such as ablation.