TY - JOUR
T1 - Pirfenidone is a cardioprotective drug
T2 - Mechanisms of action and preclinical evidence
AU - Aimo, Alberto
AU - Cerbai, Elisabetta
AU - Bartolucci, Gianluca
AU - Adamo, Luigi
AU - Barison, Andrea
AU - Lo Surdo, Giuseppa
AU - Biagini, Stefania
AU - Passino, Claudio
AU - Emdin, Michele
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/5
Y1 - 2020/5
N2 - Myocardial 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 disorders, and the wide spectrum of activity of pirfenidone, this drug has been evaluated with interest as a potential treatment for cardiac disorders. In animal studies, pirfenidone has shown cardioprotective effects across different species and in a variety of models of cardiomyopathy. In the present review we summarize the pharmacological characteristics of pirfenidone and the data from animal studies supporting its cardioprotective effects.
AB - Myocardial 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 disorders, and the wide spectrum of activity of pirfenidone, this drug has been evaluated with interest as a potential treatment for cardiac disorders. In animal studies, pirfenidone has shown cardioprotective effects across different species and in a variety of models of cardiomyopathy. In the present review we summarize the pharmacological characteristics of pirfenidone and the data from animal studies supporting its cardioprotective effects.
KW - Cardiac protection
KW - Fibrosis
KW - Inflammation
KW - Pirfenidone
KW - Pirfenidone (PubChem CID: 40632)
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U2 - 10.1016/j.phrs.2020.104694
DO - 10.1016/j.phrs.2020.104694
M3 - Article
C2 - 32061664
AN - SCOPUS:85079675508
VL - 155
JO - Pharmacological Research
JF - Pharmacological Research
SN - 1043-6618
M1 - 104694
ER -