title: [The role of glucose/TSP-1/TGFbeta1 signal pathways in diabetic cardiomyopathy].
abstract: OBJECTIVE
  Hyperglycemia could upregulate transforming growth factor-beta (TGFbeta(1)) via thrombospondin (TSP-1) and induce fibrotic renal disease in the rat in vivo and myocardial fibrosis was related to cardiac dysfunction in diabetic patients. We explored the role of glucose/TSP-1/TGFbeta(1) signal pathways in the development of diabetic cardiomyopathy (DCM).
  
  
  METHODS
  Male Wistar rats were fed with high cholesterol diet for 17 weeks, streptozocin (30 mg/kg, i.p) was given at the 28th day, rats with fasting blood glucose > or = 11.1 mmol/L by the end of the 5th week were assigned to DCM group (n = 11). Control rats (n = 8) were fed with regular chow. Fasting blood glucose (FBG) was monitored throughout the study. After hemodynamic measurements by the end of the study, myocardial collagen content was quantified in Masson-stained samples and the mRNA expressions of TSP-1 and TGFbeta(1) were detected by quantification real-time RT-PCR. The protein levels of TSP-1, active and latent TGFbeta(1) were detected by Western blot.
  
  
  RESULTS
  Compared with control group, cardiac function was decreased as shown by significantly reduced left ventricular systolic pressure, dp/dt(max) and dp/dt(min), while the myocardial collagen content was significantly increased in the DCM group (11.01 +/- 3.05 vs. 16.92 +/- 3.18, P < 0.01). The myocardial mRNA expressions of TSP-1, TGFbeta(1) and protein expressions of TSP-1, active and latent TGFbeta(1) in the DCM group were also significantly higher than those of the control group. Moreover, myocardial collagen was positively correlated to FBG (r = 0.746, P < 0.01); mRNA expressions of TSP-1 and TGFbeta(1), protein expressions of TSP-1 and active TGFbeta(1) were positively correlated to FBG and myocardial collagen (P < 0.05). However, there were no correlations between the protein expression of latent TGFbeta(1) and FBG and myocardial collagen.
  
  
  CONCLUSIONS
  The pathway of glucose/TSP-1/TGFbeta(1) might play an important role in myocardial interstitial fibrosis of DCM. It may be the basis of novel therapeutic approaches for ameliorating DCM.
authors.affiliation: Department of Cardiology, Qilu Hospital of Shandong University, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Jinan 250012, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Ya
authors.initials: Y
authors.lastname: Miao
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.forename: Hui-ping
authors.initials: HP
authors.lastname: Gong
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Meng-xiong
authors.initials: MX
authors.lastname: Tang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D019700:Thrombospondin 1 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D019700:Thrombospondin 1; D053773:Transforming Growth Factor beta1; D005947:Glucose