title: Modulating autophagy improves cardiac function in a rat model of early-stage dilated cardiomyopathy.
abstract: OBJECTIVE
  Previous studies reported that autophagy is activated in human dilated cardiomyopathy (DCM). It is still unknown whether modulating autophagy can improve cardiac function of the failing heart.
  
  
  METHODS
  We immunized rats with porcine cardiac myosin to set up a model of DCM. Rapamycin, a kind of mTOR inhibitor upregulating autophagy, was given to rats weeks after the immunization at low (1 mg/kg · day i.p.), intermediate (2 mg/kg · day i.p.) and high dose (4 mg/kg · day i.p.) for 2 weeks.
  
  
  RESULTS
  Compared to the control group (ejection fraction, EF = 81.3 ± 3.8%), the average EF decreased in both the DCM group (EF = 56.1 ± 3.3%) and the high-dose rapamycin group (EF = 55.9 ± 3.6%), but recovered in the low-/intermediate-dose rapamycin groups (EF = 64.9 ± 4.6/69.4 ± 4.4%). Phosphorylation of p70s6k and 4E-BP1 decreased and the expression of LC3BI/II increased in all rapamycin groups. Autophagic vacuoles were easily found in these groups. However, body weight was significantly reduced in the rapamycin groups. Furthermore, mortality was increased in the high-dose rapamycin group.
  
  
  CONCLUSIONS
  Rapamycin could improve cardiac function of early-stage DCM, but the effect of rapamycin turned out to be biphasic and the effective range appeared narrow.
authors: Department of Cardiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Kun
authors: K
authors: Xie
authors: Bo
authors: B
authors: Jin
authors: Yong
authors: Y
authors: Li
authors: Xinping
authors: X
authors: Luo
authors: Jun
authors: J
authors: Zhu
authors: Duan
authors: D
authors: Ma
authors: Haiming
authors: H
authors: Shi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D015431:Weight Loss / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus