Key result
Diabetic rats exhibited early cardiac changes, including increased left ventricular internal dimensions and altered molecular markers, that were independent of hypertension.
Why the study?
Does diabetes induce early cardiac remodeling independent of hypertension in a rat model?
Does diabetes induce early cardiac remodeling independent of hypertension in a rat model?
Diabetes induces early cardiac remodeling and alters the ACE/ACE2 balance independent of hypertension in a rat model, suggesting a role for increased AT1R signaling.
Diabetes may drive early LV remodeling independent of hypertension in rats; leaves open human translation and targeted interventions.
Cardiac remodeling is a key event in both diabetic and hypertensive heart diseases. In the present study, we investigated early myocardial changes in an animal model, the male Sabra rat model (SBH/y) of salt-induced hypertension-rendered diabetic with streptozotocin. Control non-diabetic (C), diabetic (D), and D or C rats made hypertensive by salt loading (DS or CS) were studied after 6 weeks. M-mode echocardiography revealed that left ventricular internal dimension during diastole and systole were significantly increased in D and DS, but not in C or CS. Concurrently, we found in D and DS an increase in cardiac beta-myosin heavy chain, atrial natriuretic peptide, skeletal alpha-actin mRNA, type III collagen, and transforming growth factor-beta. Myocardial angiotensin-converting enzyme (ACE) mRNA levels were increased while ACE2 mRNA levels were decreased in both D and DS groups. Cardiac angiotensin-1 (AT1) receptor protein levels were unchanged but the levels of phosphorylated (p) ERK and Jun-NH(2)-protein kinase (JNK) were increased in D and DS. In conclusion, we detected early cardiac changes in diabetic rats that were unrelated to hypertension. The increase in ACE, the decrease in ACE2, and the increase in cardiac pERK and pJNK suggest an increase in free angiotensin II and AT1R signaling in the diabetic myocardium as a possible mechanism contributing to cardiac remodeling in diabetes.
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Landau et al. (2008) studied Cardiac remodeling in diabetes and hypertension. Diabetes (streptozotocin-induced) and/or salt-induced hypertension vs. Control non-diabetic rats was evaluated on Cardiac remodeling (left ventricular internal dimension and molecular markers). Diabetic rats exhibited early cardiac changes, including increased left ventricular internal dimensions and altered molecular markers, that were independent of hypertension.
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