[The role of glucose/TSP-1/TGFbeta1 signal pathways in diabetic cardiomyopathy].

Objective Hyperglycemia could upregulate transforming growth factor-beta (TGFβ_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/TGFβ_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 ≥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 TGFβ_1 were detected by quantification real-time RT-PCR. The protein levels of TSP-1, active and latent TGFβ_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, TGFβ_1 and protein expressions of TSP-1, active and latent TGFβ_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 TGFβ_1, protein expressions of TSP-1 and active TGFβ_1 were positively correlated to FBG and myocardial collagen ( P 0.05). However, there were no correlations between the protein expression of latent TGFβ_1 and FBG and myocardial collagen.Conclusion The pathway of glucose/TSP-1/TGFβ_1 might play an important role in myocardial interstitial fibrosis of DCM. It may be the basis of novel therapeutic approaches for ameliorating DCM.