Doxycycline ameliorates aggregation of collagen and atrial natriuretic peptide in murine post-infarction heart.
Heart failure after myocardial infarction (MI) is associated with the aggregation of collagen and some misfolded proteins. This study was aimed to assess the therapeutic efficacy of doxycycline (Dox) in MI-induced heart failure and elucidate the potential mechanisms involved. A heart failure model of animals was established by ligating the left anterior descending coronary artery of rats. The administration of Dox via drinking water (25mg/kg/day) was initiated after surgery and lasted for two weeks. After cardiac function evaluation by echocardiography, all animals were killed to assess the aggregation of type I collagen, atrial natriuretic peptide (ANP), and the activities of matrix metalloproteinases (MMPs), autophagosomes and microtubule-associated protein 1 light chain 3 (LC3). Dox treatment significantly improved cardiac function and attenuated cardiac hypertrophy. Histological observation revealed that Dox significantly reduced the expression of collagen and ANP in the heart. Further investigation showed that Dox significantly inhibited the activities of MMP-2 and MMP-9, increased autophagosomes and enhanced LC3-II in post-infarction hearts. This study revealed that Dox treatment could promote autophagy, reduce ANP aggregation in post-infarction hearts, and inhibit MMP-2 and MMP-9 activities. Dox might act as a potential therapeutic drug for preventing proteotoxicity and cardiac dysfunction.
Department of Cardiology, Anhui Provincial Hospital of Anhui medical university, Hefei 231000, PR China.
Hongjun
H
Zhu
Department of Cardiology, Anhui Provincial Hospital of Anhui medical university, Hefei 231000, PR China.
Xianlin
X
Sun
Department of Gerontology, Yijishan Hospital of Wannan Medical College, Wuhu 241001, PR China. Electronic address: wangdeguo2005@hotmail.com.
Deguo
D
Wang
Department of Gerontology, Yijishan Hospital of Wannan Medical College, Wuhu 241001, PR China; Department of Pharmacology and Therapeutics, and Trinity College, Institute of Neuroscience, Biotechnology Building, Trinity College Dublin, Dublin 2, Ireland.
Nengwei
N
Hu
Department of Biochemistry, Wannan Medical College, Wuhu 241001, PR China.
Yao
Y
Zhang
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism*; D004318:Doxycycline / Q000494:pharmacology* / Q000627:therapeutic use; D004452:Echocardiography; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects; D051381:Rats; D020257:Ventricular Remodeling
D009320:Atrial Natriuretic Factor; D024042:Collagen Type I; D004318:Doxycycline; D020782:Matrix Metalloproteinases; D008869:Microtubule-Associated Proteins; C526109:Anxa3 protein, rat
Atrial natriuretic peptide (ANP); Autophagy; Doxycycline; Matrix metalloproteinase (MMP); Myocardial infarction (MI)