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

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.

Alcohol exposure during pregnancy causes non-compaction cardiomyopathy in offspring mice / 第三军医大学学报

Objective To investigate the relationship of alcohol exposure during pregnancy and non-compaction cardiomyopathy (NCC) in offspring mice.Methods Pregnant mice of ED3.5-ED18.5 were given 56％ alcohol by gavage at a dose of 5 mL/kg.The ED19.5 mice were sacrificed,and the heart of the fetal mice was harvested.Transmission electron microscopy (filaments,mitochondria and sarcoplasmic reticulum) and HE staining were used to verify the changes of structure and ultrastructure of the obtained myocardial tissues.Echocardiography was used to evaluate the cardiac function and ventricular myometrium of the offspring mice after growing up.Results Alcohol exposure during pregnancy caused the disorganized and dissolved myofilaments in the fetal mice.Some offspring mice (31.25％,5/16) had NCC.The ratio of non-compacted myocardium to compact myocardium at the end of systole (N/C) was 2.49 ± 0.6 in the offspring mice of the alcohol exposure group,significantly higher than that in the control offspring mice (0.62 ± 0.23,t =10.397,P =0.000).The volume of heart was decreased in the offspring mice of the alcohol exposure group while the left ventricule was enlarged.Echocardiography showed cardiac dysfunction and thickened ventricular septal/left ventricular posterior walls in the grown-up mice of the exposure group.Conclusion Large dose of alcohol exposure during pregnancy cause trabeculations and non-compaction in ventricular myocardium,and it might be one of causers for NCC in the offspring.