title: Pirfenidone attenuates cardiac fibrosis in a mouse model of TAC-induced left ventricular remodeling by suppressing NLRP3 inflammasome formation.
abstract: OBJECTIVE
  Left ventricular remodeling is a frequent complication of hypertension with no therapeutic treatment available for the subsequent onset of myocardial fibrosis. Pirfenidone is an antifibrotic small-molecular-size drug with anti-inflammatory properties that is used as a treatment for fibrotic diseases, but its effects on hypertension-induced myocardial fibrosis are unknown. Therefore, we tested whether pirfenidone could ameliorate hypertension-induced left ventricular remodeling and whether hypertension-induced NLRP3 (Nod-like receptor pyrin domain containing 3), a critical protein in NLRP3 inflammasome formation, is involved in the therapeutic mechanism.
  
  
  METHODS
  A TAC-induced mouse model of hypertension and left ventricular hypertrophy was treated with pirfenidone, and survival, collagen deposition by histopathologic examination, heart function by echocardiography, concentrations of fibrosis-related inflammatory cytokines TGF-β1, IL-1β in heart homogenate and in vitro cell cultures by ELISA, levels of ROS and inflammatory cells by flow cytometry, and levels of NLRP3 by Western blotting and immunohistochemistry were measured.
  
  
  RESULTS
  Pirfenidone increased the survival rate and attenuated myocardial fibrosis and inflammatory mediators in the TAC-induced hypertension-complicated left ventricular remodeling mouse model. The inhibition of NLRP3 expression by pirfenidone attenuated the expression of IL-1β and IL-1β-induced inflammatory and profibrotic responses.
  
  
  CONCLUSIONS
  Pirfenidone may be useful in the treatment of hypertension-induced myocardial fibrosis by inhibiting NLRP3-induced inflammation and fibrosis.
authors.affiliation: Department of Cardiology, Beijing Friendship Hospital Affiliated to the Capital Medical University, Beijing, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Wu
authors.forename: Jiawei
authors.initials: J
authors.lastname: Chen
authors.forename: Shumei
authors.initials: S
authors.lastname: Zhao
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D003094:Collagen / Q000378:metabolism; D003250:Constriction; D005355:Fibrosis / Q000517:prevention & control; D006352:Heart Ventricles; D006973:Hypertension / Q000188:drug therapy; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000517:prevention & control; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015996:Survival Rate; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D011728:Pyridones; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D003094:Collagen; C093844:pirfenidone