Gene regulation and hypertroipc responses in age-matched control and STZ-treated rats

Abstract

Calcineurin is an endogenous calcium dependent protein which is involved in the development of cardiac hypertrophy. This study investigated the role of calcineurin in the streptozotocin (STZ)- induced rat heart compared to their age-matched healthy control hearts. The calcineurin signal process is thought to be one of the major contributory pathways in the production of cardiac hypertrophy. Diabetes mellitus (DM) was induced in male Wistar rats by a single intraperitoneal injection of STZ (60 mg kg' body weight) which resulted in an experimental model of type 1 diabetes mellitus. DM was confirm.ed four days after STZ injection. The animals were humanely killed 8 weeks later for experimentation. Throughout the 8-week period, the STZ-induced diabetic rats developed symptoms of polyuria, polydipsia polyphagia and weight loss
The results of the experiments show that the STZ-induced diabetic rats displayed the following characteristics; reduced
plasma insulin levels (hypoinsulinaemia), reduced viability of the myocytes, reduced body and heart weights with significant
increases in plasma glucose concentration (hyperglycaemia) and plasma osmolality (hyperosmolality) compared to age-matched controls. All these symptoms and signs are consistent with the diabetogenic state and the values were highly significant (p c0.05).
The study also investigated the pharmacological effect of either digoxin or captopril, at a dose of 10 3 M, on the force of
contraction of isolated healthy age-matched control intact perfused hearts. The results show that the cardiac glycoside,
digoxin evoked a small increase in the force of contraction of the heart, whilst captopril, an inhibitor of angiotensin converting
enzyme (ACE), had no effect on the force of contraction.
Additionally, ventricular myocytes were isolated from the hearts and stained for NFAT and calcineurin. NFAT was identified by
immunohistochemistry and calcineurin was quantitative analysed and measured by technique of Western Blotting. Statistical
analysis was done by Mann Whitney U test for two independent samples using SPSS version 2 with p = 0.027 between diabetic and normal hearts. The results show there was an increase in the concentration of NFAT and a significant decrease in calcineurin level in the diabetic heart as compared to the age-matched controls.
Taken together the results of the study have indicated that DM is associated with reciprocal changes in levels of NFAT and
calcineurin in the heart. The NFAT content of the nuclei of the myocytes of these hearts was increased whilst the calcineurin
El concentration in the cytoplasm decreased and these may contributed to the failing heart and possibly diabetes- induced
cardiomyopathy.