The effect of melatonin on cardio fibrosis in juvenile rats with pressure overload and deregulation of HDACs

Abstract

The effect of melatonin on juveniles with cardio fibrosis is poorly understood. We investigated whether HDACs participate in the anti-fibrotic processes regulated by melatonin during hypertrophic remodeling. Abdominal aortic constriction (AAC) was employed in juvenile rats resulting in pressure overload-induced ventricular hypertrophy and melatonin was subsequently decreased via continuous light exposure for 5 weeks after surgery. AAC rats displayed an increased cross-sectional area of myocardial fibers and significantly elevated collagen deposition compared to sham-operated rats, as measured by HE and Masson Trichrome staining. Continuous light exposure following surgery exacerbated the increase in the cross-sectional area of myocardial fibers. The expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 genes were all significantly enhanced in AAC rats with light exposure relative to the other rats. Moreover, the protein level of TNF-α was also upregulated in the AAC light exposure groups when compared with the sham. However, Smad4 protein expression was unchanged in the juveniles' hearts. In contrast, beginning 5 weeks after the operation, the AAC rats were treated with melatonin (10 mg/kg, intraperitoneal injection every evening) or vehicle 4 weeks, and sham rats were given vehicle. The changes in the histological measures of cardio fibrosis and the gene expressions of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 were attenuated by melatonin administration. The results reveal that melatonin plays a role in the development of cardio fibrosis and the expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 in cardiomyocytes.

Histone deacetylase 9 downregulation decreases tumor growth and promotes apoptosis in non‐small cell lung cancer after melatonin treatment

“…Previous studies showed the great therapeutic potential of HDAC inhibitors involved in the NSCLC treatment, and recent research findings reported that new class IIa HDAC inhibitors (eg, TMP195, TMP269, LMK235) are used in the cancer treatment studies . Interestingly, melatonin treatment could ameliorate the rat myocardial fibrosis caused by abdominal aortic constriction via reducing the expression of HDAC1, HDAC2, HDAC3, HDAC4, and HDAC6 . Moreover, Wei et al found that melatonin could induce apoptosis in colorectal cancer cells by promoting HDAC4 nuclear import.…”

The crosstalk of HDAC3, microRNA-18a and ADRB3 in the progression of heart failure

“…Also, the inhibition of HDAC3 has been previously shown to suppresses myocyte hypertrophy and alleviate LVHF in animals [ 13 ]. After instilling melatonin treatment, the cardio fibrosis along with the gene expressions of HDAC1 (1, 2, 3, 4, 6) are both alleviated [ 41 ]. Furthermore, inhibition of HDAC3 can improve cell viability and alleviate apoptosis in cerebral ischemia reperfusion injury mice in diabetic state [ 42 ].…”

Rutaecarpine Ameliorates Pressure Overload Cardiac Hypertrophy by Suppression of Calcineurin and Angiotensin II

“…In the response to long-standing arterial hypertension, heart function is maintained through enlarged cardiomyocytes and increased protein synthesis, accompanied by the reactivation of the fetal gene expression, such as ANF, which are the characteristics of cardiac hypertrophy. The abdominal aorta is constricted to increase cardiac pressure overload and induce cardiac hypertrophy, which is more clinically relevant and similar to the human form of the disease [ 9 , 14 ]. Numerous studies have found that the left ventricular hypertrophy was developed on the 4th week after AAC in rats, which was similar to the results in the present study (data not shown).…”