Pirfenidone is a Cardioprotective Drug: Mechanisms of Action and Preclinical Evidence

Publication date: Available online 12 February 2020Source: Pharmacological ResearchAuthor(s): Alberto Aimo, Elisabetta Cerbai, Gianluca Bartolucci, Luigi Adamo, Andrea Barison, Giuseppa Lo Surdo, Stefania Biagini, Claudio Passino, Michele EmdinAbstractMyocardial fibrosis is an endogenous response to different cardiac insults that may become maladaptive over time and contribute to the onset and progression of heart failure (HF). Fibrosis is a direct and indirect target of established HF therapies, namely inhibitors of the renin-angiotensin-aldosterone system, but its resilience to therapy warrants a search for novel, more targeted approaches to myocardial fibrosis.Pirfenidone is a drug approved for idiopathic pulmonary fibrosis, a severe form of idiopathic interstitial pneumonias. Pirfenidone is a small synthetic molecule with high oral bioavailability, exerting an antifibrotic activity, but also anti-oxidant and anti-inflammatory effects. These effects have been attributed to the inhibition of several growth factors (in particular transforming growth factor-β, but also platelet-derived growth factor and beta fibroblast growth factor), matrix metalloproteinases, and pro-inflammatory mediators (such as interleukin-1β and tumour necrosis factor-α), and possibly also an improvement of mitochondrial function and modulation of lymphocyte activation. Given the activation of similar profibrotic pathways in lung and heart disease, the crucial role of fibrosis in several cardiac dis...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research