Abstract
Purpose: To study the role of heart and neural crest derivatives expressed 1 (HAND1) and cystathionine-beta-synthase (CBS) in the maintenance of cardiac architecture following high fat dietinduced obesity.
 Methods: Mouse models of initial and critical heart disease were established by continuous feeding of high fat diet for 7 and 12 months, respectively. The expression of HAND1 and CBS were assayed using immunohistochemistry and Western blotting.
 Results: Obesity led to mild and severe forms of heart disease which were confirmed through histological imaging. Initial obesity resulted in cardiac tissue remodeling along with initial degeneration, while critical obesity resulted in tissue hardening. The expression of HAND1 was upregulated 4.3 folds in the mild form of cardiac failure, relative to marginal expression pattern of HAND1 in control tissue. However, as the disease progressed, the expression of HAND1 was limited in serve form of cardiac failure. Moreover, the expression of cystathionine beta-synthase (CBS) was upregulated 3.7-fold in the initial form of heart failure, but was subsequently reduced in serve form of heart disease.
 Conclusion: These results reveal that in high fat diet-induced cardiac stress, the over-expressions of HAND1 and CBS at the initial stages induce extensive alterations in cardiac architecture.
Highlights
Heart failure results in progressive decreases in cardiac mechanical function
Heart disease results in arrhythmias which are linked to disruption of Ca2+ homeostasis in cardiomyocytes [2]
The actual roles of heart and neural crest derivatives expressed 1 (HAND1) and CBS expressions at different stages of obesity-induced cardiac stress were investigated in the present study
Summary
Heart failure results in progressive decreases in cardiac mechanical function. Cardiac failure involves multiple factors such as inflammation and neuro-hormonal changes, as well as lesions in cardiac, vascular smooth muscle, fibroblast and endothelial tissues [1]. It has been reported that inhibition of CBS may be a therapeutic approach for ischemic injury [14] Against this background, the actual roles of HAND1 and CBS expressions at different stages of obesity-induced cardiac stress were investigated in the present study. Dissected heart tissue was sliced into smaller sections and thoroughly washed with distilled water They were fixed in 10 % formalin solution in a container for 48 h at 40 oC. The mice fed high fat diet for 12 continuous months developed morbid obesity (mean weight = 132 ± 5 g), with thrice the weight gain of control mice of the same age (mean weight = 43 ± 2 g). The mice fed high fat diet for 7 continuous months developed cardiac tissue remodeling, with early degeneration of heart tissue (Figure 1B). The experimental data were subjected to statistical analyses using version 22.0 SPSS software (SPSS Inc, Chicago, USA)
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