Combining an enhanced tissue renin-angiotensin system with streptozotocin-induced hyperglycaemia in Ren-2 rats led to diastolic dysfunction and adverse remodeling (p<0.01 vs non-diabetic).
Does streptozotocin-induced diabetes cause diastolic dysfunction and adverse remodeling in (mRen-2)27 rats with an enhanced tissue renin-angiotensin system?
In a rodent model, the combination of an enhanced tissue renin-angiotensin system and hyperglycemia leads to the development of diabetic cardiomyopathy characterized by diastolic dysfunction and adverse remodeling.
p-value: p=<0.01
OBJECTIVE: Diabetic cardiomyopathy is an increasingly recognized cause of cardiac failure despite preserved left ventricular systolic function. Given the over-expression of angiotensin II in human diabetic cardiomyopathy, we hypothesized that combining hyperglycaemia with an enhanced tissue renin-angiotensin system would lead to the development of diastolic dysfunction with adverse remodeling in a rodent model. METHODS: Homozygous (mRen-2)27 rats and non-transgenic Sprague Dawley (SD) rats were randomized to receive streptozotocin (diabetic) or vehicle (non-diabetic) and followed for 6 weeks. Prior to tissue collection, animals underwent pressure-volume loop acquisition. RESULTS: Diabetic Ren-2 rats developed impairment of both active and passive phases of diastole, accompanied by reductions in SERCA-2a ATPase and phospholamban along with activation of the fetal gene program. Structural features of diabetic cardiomyopathy in the Ren-2 rat included interstitial fibrosis, cardiac myocyte hypertrophy and apoptosis in conjunction with increased activity of transforming growth factor-beta (p<0.01 compared with non-diabetic Ren-2 rats for all parameters). No significant functional or structural derangements were observed in non-transgenic, SD diabetic rats. CONCLUSION: These findings indicate that the combination of enhanced tissue renin-angiotensin system and hyperglycaemia lead to the development of diabetic cardiomyopathy. Fibrosis, and myocyte hypertrophy, a prominent feature of this model, may be a consequence of activation of the pro-sclerotic cytokine, transforming growth factor-beta, by the diabetic state.
Connelly et al. (Sat,) conducted a other in Diabetic cardiomyopathy. Streptozotocin (diabetic) vs. Vehicle (non-diabetic) was evaluated on Diastolic dysfunction and structural features (interstitial fibrosis, cardiac myocyte hypertrophy, apoptosis, TGF-beta activity) (p=<0.01). Combining an enhanced tissue renin-angiotensin system with streptozotocin-induced hyperglycaemia in Ren-2 rats led to diastolic dysfunction and adverse remodeling (p<0.01 vs non-diabetic).