Histone methylation is one of the key post-translational modifications that plays a critical role in various heart diseases, including diabetic cardiomyopathy. A great deal of evidence has shown that histone methylation is closely related to hyperglycemia, insulin resistance, lipid and advanced glycation end products deposition, inflammatory and oxidative stress, endoplasmic reticulum stress and cell apoptosis, and these pathological factors play an important role in the pathogenesis of diabetic cardiomyopathy. In order to provide a novel theoretical basis and potential targets for the treatment of diabetic cardiomyopathy from the perspective of epigenetics, this review discussed and elucidated the association between histone methylation and the pathogenesis of diabetic cardiomyopathy in details.
Diabetes Mellitus ; Diabetic Cardiomyopathies/pathology* ; Histones ; Humans ; Methylation ; Oxidative Stress ; Protein Processing, Post-Translational

Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy, myocardial fibrosis and diastolic dysfunction, which are uncorrelated with underlying coronary artery disease or hypertension. As an important metabolic organelle, mitochondria directly involve the process of cell growth, proliferation, signal transduction, apoptosis and so on. Recent studies have demonstrated a close correlation between the mitochondrial dysfunction and the pathogenesis of diabetic cardiomyopathy. The underlying effects of mitochondrial dysfunction in the progress of diabetic cardiomyopathy involve disturbed metabolism, oxidative stress, defective calcium handling, mitochondrial uncoupling, apoptosis, imbalance of mitochondrial quality control and regulation of MicroRNAs. Traditional Chinese medicines have been widely applied in clinic. Nowadays, more and more herbs of extracts of traditional Chinese medicines have been proved to ameliorate diabetic myocardial injury. Because the improvement of mitochondrial dysfunction has emerged as a promising therapeutic strategy, this review summarizes these effects of mitochondrial dysfunction in diabetic cardiomyopathy, and discusses the intervention studies of traditional Chinese medicine in the field, in expectation to provide new ideas for DCM prevention and treatment.
Diabetic Cardiomyopathies ; drug therapy ; pathology ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Mitochondria ; pathology ; Myocardium

OBJECTIVE: To investigate the nucleolus expression in the diabetic cardiomyopathy. METHODS: The rats were divided into a control group and a type II diabetic cardiomyopathy group (model group). In the model group, rats were fed with high-fat and high-sugar food (rats were intravenously injected with 60 mg/kg chain urea with cephalosporins in the 5th and 6th weeks in mice). The level of blood glucose was determined at the end of 8th week and the level of fasting blood glucose was examined at the end of 20th week. The ratio of the heart mass and body mass was calculated, and the pathological changes in myocardial morphology were observed. The immunohistochemical method and Western blot were used to detect the expression level of myocardial nucleolin. RESULTS: The level of fasting blood glucose was significantly increased in the diabetic model group than that in the control group (P<0.05). Rats in the model group were found hypertrophic cardic cells, with fracture, dissolusion, and disordered arrangement. Immunohistochemical staining and Western blot showed the protein levels of myocardial nucleolin in the model group were obviously higher than those in the control group (P<0.05). CONCLUSION Nucleolin may play a role in the pathogenesis and development of the diabetic cardiomyopathy.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; metabolism ; Diabetic Cardiomyopathies ; metabolism ; Myocardium ; pathology ; Phosphoproteins ; metabolism ; RNA-Binding Proteins ; metabolism ; Rats

OBJECTIVE: To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyopathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. METHODS: Sixty Sprague-Dawley (SD) rats were randomly divided into six groups: a normal control group (NC), an obesity group (OB), a diabetic cardiomyopathy group (DCM), a tea polyphenol group (TP), an obesity tea polyphenol treatment group (OB-TP), and a diabetic cardiomyopathy tea polyphenol treatment group (DCM-TP). After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ultrasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-II, SQSTM1/p62, and Beclin-1 were determined by Western blotting. RESULTS: Compared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-II/I and Beclin-1 increased obviously, whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups (P<0.05). CONCLUSIONS Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.
Animals ; Autophagy ; drug effects ; Beclin-1 ; analysis ; Blood Glucose ; analysis ; Body Weight ; Diabetic Cardiomyopathies ; drug therapy ; pathology ; physiopathology ; Lipids ; blood ; Male ; Myocardium ; pathology ; Polyphenols ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tea ; chemistry

OBJECTIVETo observe the dynamic expression of calcium-sensing receptor(CaSR) in myocardium of diabetic rats.

METHODSThirty male Wistar rats were randomly divided into 3 groups including control, diabetic-4 week and diabetic-8 week groups(n = 10). The type 2 diabetes mellitus models were established by intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) after high-fat and high-sugar diet for one month. The cardiac morphology was observed by electron microscope. Western blot analyzed the expression of CaSR, phospholamban (PLN), a calcium handling regulator, and Ca+-ATPase(SERCA) in cardiac tissues.

RESULTSCompared with control group, the expressions of CaSR and SERCA were decreased, while the expression of PLN was significantly increased in a time-dependent manner in diabetic groups. Meanwhile diabetic rats displayed abnormal cardiac structure.

CONCLUSIONThese results indicate that the CaSR expression of myocardium is reduced in the progression of DCM, and its potential mechanism may be related to the imnaired intracellular calcium homeostasis.

Animals ; Calcium-Binding Proteins ; metabolism ; Diabetes Mellitus, Experimental ; complications ; Diabetes Mellitus, Type 2 ; Diabetic Cardiomyopathies ; metabolism ; physiopathology ; Disease Progression ; Heart ; physiopathology ; Male ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Wistar ; Receptors, Calcium-Sensing ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Streptozocin

OBJECTIVEThe beneficial effects of silymarin have been extensively studied in the context of inflammation and cancer treatment, yet much less is known about its therapeutic effect on diabetes. The present study was aimed to investigate the cytoprotective activity of silymarin against diabetes-induced cardiomyocyte apoptosis.

METHODSRats were randomly divided into: control group, untreated diabetes group and diabetes group treated with silymarin (120 mg/kg•d) for 10 d. Rats were sacrificed, and the cardiac muscle specimens and blood samples were collected. The immunoreactivity of caspase-3 and Bcl-2 in the cardiomyocytes was measured. Total proteins, glucose, insulin, creatinine, AST, ALT, cholesterol, and triglycerides levels were estimated.

RESULTSUnlike the treated diabetes group, cardiomyocyte apoptosis increased in the untreated rats, as evidenced by enhanced caspase-3 and declined Bcl-2 activities. The levels of glucose, creatinine, AST, ALT, cholesterol, and triglycerides declined in the treated rats. The declined levels of insulin were enhanced again after treatment of diabetic rats with silymarin, reflecting a restoration of the pancreatic β-cells activity.

CONCLUSIONThe findings of this study are of great importance, which confirmed for the first time that treatment of diabetic subjects with silymarin may protect cardiomyocytes against apoptosis and promote survival-restoration of the pancreatic β-cells.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Glucose ; Cholesterol ; blood ; Creatinine ; blood ; Diabetes Mellitus, Experimental ; complications ; Diabetic Cardiomyopathies ; prevention & control ; Heart ; drug effects ; Immunohistochemistry ; Insulin ; blood ; Male ; Myocardium ; pathology ; Myocytes, Cardiac ; drug effects ; Rats ; Silymarin ; pharmacology ; Triglycerides ; blood

OBJECTIVETo study the protective effect of the Mixture of Shengmai Powder and Danshen Decoction (, abbreviated as the Mixture) in the rat model with type 2 diabetic cardiomyopathy in the rat model with type 2 diabetic cardiomyopathy, abbreviated as the Mixture) in the rat model with type 2 diabetic cardiomyopathy (DCM).

METHODSForty-two SD rats with DCM model, established by the combination of insulin resistance by a high-fat diet with the damage of pancreatic islet β cells by intraperitoneal injection of high dose streptozotocin (50 mg/kg) once, were evaluated in the damage of the myocardium by electrocardiogram at the end of 12 weeks of grouping and intervention administration; the extent of damage in the myocardial subcellular structure was observed by electron microscopy; the content of myocardial collagen in the left cardiac ventricle was quantified by Masson staining test; the myocardial cell apoptosis was determined by TUNEL; the changes in the mRNA expression levels of thrombospodin-1 (TSP-1) and tribbles homolog 3 (TRB-3) by real-time quantitative PCR, the expression levels of myocardial TSP-1, tumor growth factorβ1 (TGF-β1), TRB-3, and chymase were detected by immunohistochemistry, and the changes in the expression levels of myocardial TSP-1, active-TGF-β1 (A-TGF-β1) and latent-TGF-β1 (L-TGF-β1) protein were tested by Western blotting.

RESULTSCompared with the control group, the myocardial tissue was less damaged, and the extent of damage in the myocardial subcellular structure was less; the collagen fiber content and the cell apoptosis were reduced; the expression levels of TSP-1mRNA and TRB-3 mRNA, the expression levels of myocardial TSP-1, TGF-β1, TRB-3, and chymase, as well as the average expression levels of the myocardial TSP-1, A-TGFβ1, and L-TGF-β1 protein were decreased in the Mixture group.

CONCLUSIONThe Mixture of Shengmai Powder and Danshen Decoction could inhibit the process of myocardial fibrosis in the rat myocardium of DCM through multiple pathways and significantly delay the genesis and progress of DCM in hyperglycemic rats.

Animals ; Cytoprotection ; drug effects ; Diabetes Mellitus, Experimental ; complications ; drug therapy ; Diabetic Cardiomyopathies ; pathology ; prevention & control ; Disease Models, Animal ; Drug Combinations ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Heart ; drug effects ; Male ; Myocardium ; cytology ; pathology ; Rats ; Rats, Sprague-Dawley ; Streptozocin

OBJECTIVETo investigate the effects of icariin on cardiac functions and mitochondrial oxidative stress in streptozotocin (STZ)-induced diabetic rats.

METHODMale SD rats were randomly divided into normal control group, icariin control group, diabetic group, and diabetic groups administered with a low dose (30 mL x kg(-1) x d(-1), ig) or a high dose (120 mL x kg(-1) d(-1), ig) of icariin for 8 weeks. The body weight, blood glucose, cardiac functions, left ventricular weight, and myocardial collagen level were assayed. The cardiac mitochondrial reactive oxygen species (ROS) level, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were measured.

RESULTTreatment with icariin reduced the losing of body weight in diabetic rats. Icariin markedly reduced the ratio of ventricular weight and body weight, increased the left ventricular develop pressure and +/- dp/dt(max), and decreased the left ventricular end diastolic pressure in diabetic rats. The myocardial collagen and the level of cardiac mitochondrial ROS in diabetic rats were all markedly reduced by icariin. Furthermore, high dose of icariin significantly decreased the mitochondrial MDA level and increased SOD activity in diabetic rat hearts.

CONCLUSIONTreatment with icariin for 8 weeks markedly improved the cardiac function, which may be related to reducing mitochondrial oxidative stress injuries in diabetic rats.

Animals ; Body Weight ; drug effects ; Collagen ; drug effects ; metabolism ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; metabolism ; pathology ; Diabetes Mellitus, Type 1 ; drug therapy ; metabolism ; pathology ; Diabetic Cardiomyopathies ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Enteral Nutrition ; Flavonoids ; administration & dosage ; Heart Ventricles ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Mitochondria, Heart ; drug effects ; metabolism ; pathology ; Organ Size ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Streptozocin ; Superoxide Dismutase ; drug effects ; metabolism

This article aimed at exploring the effects and protective mechanism of β-CM7 on renin angiotensin system (RAS) in diabetic rats myocardial tissue. We divided 32 male SD rats into 4 groups: control group, diabetic model control group, insulin (3.7x10(-8) mol/d) treatment group and β-CM7 (7.5x10(-8) mol/d) treatment group. After 30 days, all rats were decapitated and myocardical tissues were collected immediately. After injection, β-CM7 could decrease the content of Ang II, increase the content of Angl-7. And β-CM7 could improve the mRNA of AT1 receptor and Mas receptor. β-CM7 also could improve the mRNA of ACE and ACE2, enhance the activity of ACE and ACE2. These data confirmed tli β-CM7 could activate ACE2-Angl-7-Mas axis, negative passage in RAS, to inhibit the expression ACE mnRiJA and protein in rat myocardium, alleviate the myocardial tissue damage induced by Ang II. The effect of β-CM7 on inhibiting myocardium damage might be related to ACE/ACE2 passageway.
Angiotensin II ; metabolism ; Animals ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetic Cardiomyopathies ; drug therapy ; Endorphins ; pharmacology ; Male ; Myocardium ; metabolism ; pathology ; Peptide Fragments ; pharmacology ; Peptidyl-Dipeptidase A ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Renin-Angiotensin System

BACKGROUNDThe development of diabetic cardiomyopathy is multifactorial. Insulin resistance (IR) and excessive activity of the renin-angiotensin system are confirmed reasons for diabetic cardiomyopathy. Renin-angiotensin system (RAS) inhibitors can reduce tissue Ang II levels, with beneficial effects on cardiovascular function. Therefore, in type-2 diabetes mellitus (T2DM), blockade of the RAS may have the function of protecting against diabetic cardiomyopathy through increasing insulin sensitivity and inhibiting excessive activity of RAS. However, this has not been confirmed.

METHODSThe effect of valsartan, an angiotensin receptor blocker (ARB), on diabetic cardiomyopathy in the presence of T2DM was studied. Wistar rats with T2DM and T2DM treated with valsartan were studied. Glucose infusion rates (GIR), index of IR, heart weight, the heart weight-to-body weight ratio (HW/BW), myocardial apoptotic index, cardiac hydroxyprolin content, and cardiac tissue collagen type I and collagen type III content were measured.

RESULTSGIR in T2DM rats and T2DM rats treated with valsartan decreased (P < 0.01). In T2DM rats treated with valsartan, heart weight, myocardial apoptotic index, cardiac hydroxyprolin content, and cardiac tissue collagen type I and collagen type III content were higher than in control rats, but lower than in T2DM rats. In rats with T2DM, GIR was negatively and significantly correlated with all the variables. However, in T2DM rats treated with valsartan or normal control rats, none of the correlations was significant.

CONCLUSIONSIn the presence of T2DM, diabetic cardiomyopathy is related with IR. Valsartan can not alleviate IR, but can protect against diabetic cardiomyopathy and remove the correlation between IR and diabetic cardiomyopathy.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Apoptosis ; Collagen Type I ; analysis ; Collagen Type III ; analysis ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Diabetic Cardiomyopathies ; prevention & control ; Hydroxyproline ; analysis ; Insulin Resistance ; Male ; Myocardium ; chemistry ; pathology ; Rats ; Rats, Wistar ; Tetrazoles ; therapeutic use ; Valine ; analogs & derivatives ; therapeutic use ; Valsartan