Abstract
We found that curcumin, a p300 histone acetyltransferase (HAT) inhibitor, prevents cardiac hypertrophy and systolic dysfunction at the stage of chronic heart failure in Dahl salt-sensitive rats (DS). It is unclear whether curcumin suppresses the development of hypertension-induced left ventricular hypertrophy (LVH) with a preserved ejection fraction. Therefore, in this study, we randomized DS (n = 16) and Dahl salt-resistant (DR) rats (n = 10) at 6 weeks of age to either curcumin or vehicle groups. These rats were fed a high-salt diet and orally administrated with 50 mg/kg/d curcumin or its vehicle for 6 weeks. Both curcumin and vehicle treatment groups exhibited similar degrees of high-salt diet-induced hypertension in DS rats. Curcumin significantly decreased hypertension-induced increase in posterior wall thickness and LV mass index, without affecting the systolic function. It also significantly reduced hypertension-induced increases in myocardial cell diameter, perivascular fibrosis and transcriptions of the hypertrophy-response gene. Moreover, it significantly attenuated the acetylation levels of GATA4 in the hearts of DS rats. A p300 HAT inhibitor, curcumin, suppresses the development of hypertension-induced LVH, without affecting blood pressure and systolic function. Therefore, curcumin may be used for the prevention of development of LVH in patients with hypertension.
Highlights
Heart failure (HF) is the final stage of cardiovascular diseases and the mortality and morbidity of severe HF are still high [1,2]
We investigated whether curcumin exhibited any beneficial effects on hypertension-induced left ventricular hypertrophy (LVH) in the Dahl salt-sensitive (DS) and salt-resistant (DR) rats
The left ventricle (LV) end-diastolic dimension (LVEDD), endsystolic dimension (LVESD), interventricular septum thickness (IVST) and posterior wall thickness (PWT) were measured using M-mode tracing from the short-axis view of the LV at the level of papillary muscle
Summary
Heart failure (HF) is the final stage of cardiovascular diseases and the mortality and morbidity of severe HF are still high [1,2]. LVH is a compensatory reaction, which eventually lead to maladaptive LVH and pathological remodeling with cardiac dysfunction [3] This process causes the development of HF. Chronic stresses, such as hypertension and myocardial infarction (MI), up-regulated cellular signaling pathways, increasing the expression levels of p300, a transcriptional co-activator and enhancing the activity of its histone acetyltransferase (HAT) enzyme in cardiomyocytes [7,8]. The cooperation of p300/GATA4 and acetylation of GATA4 are critical events in cardiomyocyte hypertrophy and the development of heart failure [9,13,14] Based on these results, p300-HAT activity may be used as a novel pharmacological target for HF [15]. We investigated whether curcumin exhibited any beneficial effects on hypertension-induced LVH in the Dahl salt-sensitive (DS) and salt-resistant (DR) rats
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