AIM: To study whether calcium-modulating proteins CASQ2, FKBP12.6 and SERCA2a participate in diabetic cardiomyopathy, and whether the beneficial actions of testosterone, sildenafil or fructose diphosphate Sr (FDP-Sr) in the treatment of diabetic cardiomyopathy result from suppressing these molecules. METHODS: Fifty male Sprague-Dawley (SD) rats were divided into five groups. Except for the normal group (non-diabetic), the other four groups were injected with streptozotocin (STZ, 60 mg/kg, ip) to induce diabetes. Four weeks after STZ injection, the four groups received sildenafil (12 mg·kg(-1)·d(-1), ig, for 4 week), FDP-Sr (200 mg/kg, ig, for 4 week), testosterone propionate (4 mg·kg(-1)·d(-1), sc, for 4 week), or no treatment, respectively. RESULTS: In the diabetic rats, blood glucose, free fatty acids, triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) were significantly increased, while high-density lipoprotein cholesterol (HDL-C) was significantly reduced, as compared to the non-diabetic rats. Cardiac dysfunction and myocardial hypertrophy of the diabetic rats were associated with increased mRNA and protein expression of iNOS, OBRb, and PKCɛ, while expression of CASQ2, SERCA2a, and FKBP12.6 was significantly down-regulated. Sildenafil and FDP-Sr, but not testosterone, significantly attenuated the biomarker abnormalities, without changing the metabolic abnormalities. CONCLUSION: CASQ2, FKBP12.6 and SERCA2a were down-regulated in diabetic cardiomyopathy. Sildenafil and FDP-Sr, but not testosterone, attenuated the cardiac dysfunction in diabetic cardiomyopathy, without changing the metabolic abnormalities, which may results from inhibiting oxidative and inflammatory cytokines and improving calcium homeostasis.
AIM: To study whether calcium-modulating proteins CASQ2, FKBP12.6 and SERCA2a participate in diabetic cardiomyopathy, and whether the beneficial actions of testosterone, sildenafil or fructose diphosphate Sr (FDP-Sr) in the treatment of diabetic cardiomyopathy result from suppressing these molecules. METHODS: Fifty male Sprague-Dawley (SD) rats were divided into five groups. Except for the normal group (non-diabetic), the other four groups were injected with streptozotocin (STZ, 60 mg/kg, ip) to induce diabetes. Four weeks after STZ injection, the four groups received sildenafil (12 mg·kg(-1)·d(-1), ig, for 4 week), FDP-Sr (200 mg/kg, ig, for 4 week), testosterone propionate (4 mg·kg(-1)·d(-1), sc, for 4 week), or no treatment, respectively. RESULTS: In the diabeticrats, blood glucose, free fatty acids, triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) were significantly increased, while high-density lipoprotein cholesterol (HDL-C) was significantly reduced, as compared to the non-diabeticrats. Cardiac dysfunction and myocardial hypertrophy of the diabeticrats were associated with increased mRNA and protein expression of iNOS, OBRb, and PKCɛ, while expression of CASQ2, SERCA2a, and FKBP12.6 was significantly down-regulated. Sildenafil and FDP-Sr, but not testosterone, significantly attenuated the biomarker abnormalities, without changing the metabolic abnormalities. CONCLUSION:CASQ2, FKBP12.6 and SERCA2a were down-regulated in diabetic cardiomyopathy. Sildenafil and FDP-Sr, but not testosterone, attenuated the cardiac dysfunction in diabetic cardiomyopathy, without changing the metabolic abnormalities, which may results from inhibiting oxidative and inflammatory cytokines and improving calcium homeostasis.
Authors: Antonio Mancini; Erika Leone; Roberto Festa; Giuseppe Grande; Andrea Silvestrini; Laura de Marinis; Alfredo Pontecorvi; Giulio Maira; Gian Paolo Littarru; Elisabetta Meucci Journal: J Androl Date: 2008-07-17
Authors: Athanasios Charalampopoulos; Luke S Howard; Ioanna Tzoulaki; Wendy Gin-Sing; Julia Grapsa; Martin R Wilkins; Rachel J Davies; Petros Nihoyannopoulos; Susan B Connolly; J Simon R Gibbs Journal: Pulm Circ Date: 2014-12 Impact factor: 3.017