Therapeutic targets of fibrosis: Translational advances and current challenges

Abstract

In a physiological context, the extracellular matrix (ECM) provides an important scaffold for organs. Dysregulation of ECM in disease conditions, characterised by excess deposition of connective tissue and extracellular matrix in response to a pathological insult, is a key driver of disease progression in multiple organs. The resultant fibrosis is predominantly an irreversible process and directly contributes to, and exacerbates, dysfunction of an affected organ. This is particularly paramount in the kidney, liver, heart and lung. A hybrid Joint Meeting of NC‐IUPHAR and British Pharmacological Society was held in Paris and via a webinar in November 2020, when two successive sessions were devoted to translational advances in fibrosis as a therapeutic target. On the upsurge of response to these sessions, the concept of a special themed issue on this topic emerged, and is entitled Translational Advances in Fibrosis as a Therapeutic Target. In this special issue, we seek to provide an up‐to‐date account of the diverse molecular mechanisms and causal role that fibrosis plays in disease progression (contributing to, and exacerbating, dysfunction of affected organs). Recent developments in the understanding of molecular targets involved in fibrosis, and how their actions can be manipulated therapeutically, are included.

Targeting Interactions between Fibroblasts and Macrophages to Treat Cardiac Fibrosis

“…Myocardial fibrosis is pervasive in heart diseases of many pathologic origins and is associated with the occurrence of adverse cardiovascular events and worsened patient outcomes. However, there is no known treatment for alleviating fibrosis in the heart [108]. The drugs currently used in the treatment of heart failure, including angiotensin receptor-neprilysin inhibitors (ARNI) [109,110], sodium-glucose cotransporter-2 inhibitors (SGLT2i) [111,112], and spironolactone [113], have been shown to be only mildly effective in alleviating cardiac fibrosis and improving ventricular remodeling.…”