title: The Effects of Carvedilol on Cardiac Function and the AKT/XIAP Signaling Pathway in Diabetic Cardiomyopathy Rats.
abstract: OBJECTIVE
  Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction, myocardial inflammation, interstitial fibrosis and cardiomyocytes apoptosis. The present study aimed to investigate the effects of carvedilol on cardiac function and the AKT/XIAP signaling pathway in DCM rats.
  
  
  METHODS
  Male Wistar rats were randomly divided into 3 groups: the control group, diabetic mellitus (DM) group and DM with carvedilol treatment group. DM rats were induced by streptozotocin accompanied by high energy intake. Carvedilol was orally administered at a dose of 10 mg/kg/day. After 16 weeks, the interrelated blood data were detected by biochemical analysis. Cardiac function was evaluated by echocardiography and the serum NT-proBNP level. The changes of myocardium ultrastructural and fibrosis were determined by electron microscopy and Masson's staining. Apoptotic cells were examined by TUNEL staining and interrelated proteins were measured by immunohistochemical and Western blots.
  
  
  RESULTS
  Rats in the DM group showed significant serum elevation of glucose, cholesterol, triglyceride, NT-proBNP, IL-1β and TNF-α, along with decreased cardiac function. Moreover, in the DM group, the levels of myocardial apoptosis and fibrosis were all increased accompanied by upregulation of caspase-3 and downregulation of phos-AKT and phos-XIAP, whereas carvedilol treatment prevented or reversed all the changes without influencing plasma levels of glucose, cholesterol and triglyceride.
  
  
  CONCLUSIONS
  The AKT/XIAP signaling pathway may be involved in DCM. Carvedilol can improve cardiac function, possibly not only by upregulating the AKT/XIAP antiapoptotic signaling pathway and subsequently attenuating myocardial fibrosis, but also through suppressing the myocardial inflammation response.
authors: Department of Internal Medicine, Hebei Medical University, Shijiazhuang, China.
authors: Wencheng
authors: W
authors: Zheng
authors: Xiaoming
authors: X
authors: Shang
authors: Chunlai
authors: C
authors: Zhang
authors: Xiang
authors: X
authors: Gao
authors: Barry
authors: B
authors: Robinson
authors: Jing
authors: J
authors: Liu
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D053148:Caspase 3 / Q000097:blood; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D004452:Echocardiography; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011412:Propanolamines / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D002227:Carbazoles; D051034:Inhibitor of Apoptosis Proteins; D010446:Peptide Fragments; D011412:Propanolamines; C494837:Xiap protein, rat; C109794:pro-brain natriuretic peptide (1-76); D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3