Study on complement factor D inhibitor Danicopan ameliorating ventricular remodeling in mice after myo-cardial infarction

Jin Shuhui; Shao Yihui; Zhang Congcong

doi:10.3760/j.issn.1673-4777.2026.03.004

Abstract：Objective To investigate the effects of Danicopan,a complement factor D(CFD)inhibitor,on cardiac function,myocardial hypertrophy and myocardial fibrosis in mice after myocardial infarction(MI).Methods C57BL/6 mice were randomly divided into sham operation group,MI control group and MI+Danicopan group.MI model was established by ligating the left anterior descending coronary artery.From the day of operation,mice in the MI+Danicopan group were intraperitoneally injected with Danicopan(10 mg/kg),while those in the MI control group were injected with an equal volume of phosphate-buffered saline,twice a week for 3 consecutive weeks.Mice in the sham operation group only received thoracotomy without ligation of the left anterior descending coronary artery and no drug administration.After the intervention,echocardiography was performed to evaluate cardiac function.Cardiac tissues were collected for wheat germ agglutinin staining to observe the cross-sectional area of cardiomyocytes,and Masson's trichrome staining to analyze collagen deposition and calculate the percentage of fibrotic area.Results The left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in the MI control group were significantly lower than those in the sham operation group[(21.3±1.7)％vs(68.3±2.4)％,(9.5±1.0)％vs(40.7±3.9)％],while the LVEF and LVFS in the MI+Danicopan group[(46.2±12.3)％,(23.0±7.3)％]were significantly higher than those in the MI control group(all P＜0.05).Pathological observations showed that Danicopan administration could significantly alleviate the degree of cardiomyocyte hypertrophy induced by MI and reduce the overall collagen volume fraction of myocardial tissue.Conclusion Danicopan,a CFD inhibitor,can significantly improve cardiac function,and alleviate pathological cardiomyocyte hypertrophy and interstitial fibrosis in mice with MI,suggesting that it may serve as a potential drug for the treatment of ventricular remodeling after MI.