Metabolic syndrome and diabetes are associated with increased risk of cardiac dysfunction independently of underlying coronary artery disease. The underlying pathogenesis is partially understood but accumulating evidence suggests that alterations of cardiac energy metabolism might contribute to the development of contractile dysfunction. Recent findings suggest that myocardial mitochondrial dysfunction may play an important role in the pathogenesis of cardiac contractile dysfunction in type 2 diabetes. This review is focused on evaluating mechanisms for the mitochondrial abnormalities that may be involved in the development and progression of cardiac dysfunction in diabetes.
Coronary Artery Disease ; Diabetic Cardiomyopathies ; Energy Metabolism ; Mitochondria

microRNAs are one kind of endogenous no-encoding RNA with about 22 nucleotides in length, and inhibited the translation of mRNAs by partially complementary binding to the 3' UTR of target mRNAs in the post-transcriptional level. Recent research shows that miRNAs function in the physiological and pathological processes of heart, especially involved in the occurrence and progress of arrhythmias. Abnormal miRNAs alters the protein expression of ion channels, causes the cardiac dysfunction, and triggers heart arrhythmias. The article summarized recent advances about roles of miRNA in arrhythmias and related cardiomyopathy, and discussed the therapeutic potential of miRNAs for heart diseases.
Arrhythmias, Cardiac ; genetics ; metabolism ; Cardiomyopathies ; genetics ; metabolism ; Humans ; MicroRNAs ; genetics ; metabolism

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with highly heterogeneous clinical symptoms, and its incidence has been increasing in recent years. Compared with heart failure with reduced ejection fraction (HFrEF), HFpEF has a worse prognosis. Traditional therapies targeting the internal mechanisms of the heart show limited or inefficacy on HFpEF, and new therapeutic targets for HFpEF are expected to be found by focusing on the extracardiac mechanisms. Recent studies have shown that cardiopulmonary pathophysiological interaction exacerbates the progression of HFpEF. Hypertension, systemic vascular injury, and inflammatory response lead to coronary microvascular dysfunction, myocardial hypertrophy, and coronary microvascular remodeling. Acute kidney injury affects myocardial energy production, induces oxidative stress and catabolism of myocardial protein, which leads to myocardial dysfunction. Liver fibrosis mediates heart injury by abnormal protein deposition and inflammatory factors production. Skeletal muscle interacts with the sympathetic nervous system by metabolic signals. It also produces muscle factors, jointly affecting cardiac function. Metabolic syndrome, gut microbiota dysbiosis, immune system diseases, and iron deficiency promote the occurrence and development of HFpEF through metabolic changes, oxidative stress, and inflammatory responses. Therefore, the research on the extracardiac mechanisms of HFpEF has certain implications for model construction, mechanism research, and treatment strategy formulation.
Humans ; Heart Failure/diagnosis* ; Stroke Volume/physiology* ; Myocardium/metabolism* ; Cardiomyopathies/metabolism* ; Hypertension ; Ventricular Function, Left

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

Cardiovascular diseases account for approximately 80% of deaths among individuals with diabetes mellitus, with diabetic cardiomyopathy as the major diabetic cardiovascular complication. Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy, fibrosis, apoptosis, and other pathophysiological changes. Although glycemic control has long been at the center of diabetes therapy, multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes. This finding indicates that hyperglycemic stress persists in the cardiovascular system of patients with diabetes even if blood glucose level is tightly controlled to the normal level. This process is now referred to as hyperglycemic memory (HGM) phenomenon. We briefly reviewed herein the current advances that have been achieved in research on the underlying mechanisms of HGM in diabetic cardiomyopathy.
Cardiovascular Diseases ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Cardiomyopathies/etiology* ; Humans ; Hyperglycemia/metabolism* ; Multicenter Studies as Topic

OBJECTIVEHyperglycemia could upregulate transforming growth factor-beta (TGFbeta(1)) via thrombospondin (TSP-1) and induce fibrotic renal disease in the rat in vivo and myocardial fibrosis was related to cardiac dysfunction in diabetic patients. We explored the role of glucose/TSP-1/TGFbeta(1) signal pathways in the development of diabetic cardiomyopathy (DCM).

METHODSMale Wistar rats were fed with high cholesterol diet for 17 weeks, streptozocin (30 mg/kg, i.p) was given at the 28th day, rats with fasting blood glucose > or = 11.1 mmol/L by the end of the 5th week were assigned to DCM group (n = 11). Control rats (n = 8) were fed with regular chow. Fasting blood glucose (FBG) was monitored throughout the study. After hemodynamic measurements by the end of the study, myocardial collagen content was quantified in Masson-stained samples and the mRNA expressions of TSP-1 and TGFbeta(1) were detected by quantification real-time RT-PCR. The protein levels of TSP-1, active and latent TGFbeta(1) were detected by Western blot.

RESULTSCompared with control group, cardiac function was decreased as shown by significantly reduced left ventricular systolic pressure, dp/dt(max) and dp/dt(min), while the myocardial collagen content was significantly increased in the DCM group (11.01 +/- 3.05 vs. 16.92 +/- 3.18, P < 0.01). The myocardial mRNA expressions of TSP-1, TGFbeta(1) and protein expressions of TSP-1, active and latent TGFbeta(1) in the DCM group were also significantly higher than those of the control group. Moreover, myocardial collagen was positively correlated to FBG (r = 0.746, P < 0.01); mRNA expressions of TSP-1 and TGFbeta(1), protein expressions of TSP-1 and active TGFbeta(1) were positively correlated to FBG and myocardial collagen (P < 0.05). However, there were no correlations between the protein expression of latent TGFbeta(1) and FBG and myocardial collagen.

CONCLUSIONThe pathway of glucose/TSP-1/TGFbeta(1) might play an important role in myocardial interstitial fibrosis of DCM. It may be the basis of novel therapeutic approaches for ameliorating DCM.

Animals ; Cardiomyopathies ; etiology ; metabolism ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Glucose ; metabolism ; Male ; Myocardium ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction ; Thrombospondin 1 ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo investigate the changes in aquaporin-1 (AQP-1) expression in myocardium of scalded rats in early stage of a burn injury, and to analyze its relationship with myocardial edema.

METHODSThirty-six healthy Wistar rats were divided into normal control (n = 6, without scald) and scald (n = 30) groups according to the random number table. Rats in scald group were inflicted with 30%TBSA full-thickness scald on the back, and intraperitoneally injected with Ringer's solution for antishock treatment. Myocardium tissue from left ventricle and serum specimen in rats of scald group were collected at post scald hours (PSH) 2, 8, 12, 24, and 48 (with 6 rats at each time point). Myocardial water ratio was determined by dry-wet weight method. The distribution of AQP-1 protein in myocardium was observed with immunohistochemical staining. The expression of myocardial AQP-1 mRNA was assessed with quantitative real-time PCR. The serum content of cardiac troponin-I (cTnI) was determined with ELISA. The rats in normal control group were detected with above-mentioned method. Data were processed with one way analysis of variance and LSD test. Correlation analysis was performed between AQP-1 mRNA and myocardial water ratio, AQP-1 mRNA and the serum content of cTnI in scald group at each time point.

RESULTSCompared with that in normal control group, the myocardial water ratio in scald group was markedly increased during PSH 8-48 (P values all below 0.01), and it peaked at PSH 12 [(80.79 ± 0.12)%]. In both groups, AQP-1 was mainly expressed in endothelial cells of capillaries and pericellular membrane of myocardial cells. The expression of AQP-1 in scald group was markedly increased from PSH 2 to PSH 48. The expression of myocardial AQP-1 mRNA in scald group was markedly higher from PSH 2 to PSH 48 than that in normal control group (P values all below 0.01), and it peaked at PSH 12 [(6.2 ± 0.7)%]. The serum content of cTnI in scald group was obviously higher from PSH 2 to PSH 48 than that in normal control group (P values all below 0.01), and it peaked at PSH 12 [(5.83 ± 0.51) µg/L]. There were statistically positive correlations between AQP-1 mRNA expression and myocardial water ratio (r = 0.849, P < 0.01), AQP-1 mRNA expression and the serum content of cTnI (r = 0.973, P < 0.01) in scald group.

CONCLUSIONSAQP-1 may play a key role in the development of myocardial edema in rats with scald.

Animals ; Aquaporin 1 ; metabolism ; Burns ; metabolism ; pathology ; Cardiomyopathies ; metabolism ; Disease Models, Animal ; Edema ; metabolism ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Wistar ; Troponin I ; blood

OBJECTIVETo explore the expression of Toll-like receptor 4 (TLR4) and tumor necrosis factor-α (TNF-α) on peripheral-blood mononuclear cells (PBMCs) and their correlation with myocardial perfusion in patients with diabetic cardiomyopathy (DCM).

METHODSThe expression of TLR4 and TNF-α mRNA on PBMCs were examined by SYBR Green I real-time quantitative reverse transcription polymerase chain reaction (RT-PCR), the levels of TLR4 and TNF-α were examined by flow cytometric analysis and enzyme-linked immuno sorbent assay (ELISA) on DCM group (n = 20), Type 2 diabetic group (n = 22) and control group (n = 20). Myocardial perfusion was visualized by single-photon emission computed tomography (SPECT).

RESULTSThe expressions of TLR4 and TNF-α mRNA/protein on PBMCs in DCM group were significantly higher than in Type 2 diabetic group, and higher in Type 2 diabetic group than in control groups (P < 0.05); summed stress score (SSS) and summed rest score (SRS) of myocardial perfusion in DCM group were significantly higher than in Type 2 diabetic group, and higher in Type 2 diabetic group than in control groups (P < 0.01). The expression of TLR4, TNF-α was positively correlated with SSS (r = 0.75, P < 0.05; r = 0.931, P < 0.005) and SRS (r = 0.78, P < 0.005; r = 0.789, P < 0.005). SSS and SRS in DCM group were also positively correlated with soluble vascular cell adhesion molecule-1 (sVCAM-1) (r = 0.728, P < 0.005; r = 0.738, P < 0.005) but there was no correlation between SSS and SRS and brain natriuretic peptide, LVEF, E/A, HbA1c, FBG, FIN and LDL-C (P > 0.05).

CONCLUSIONThe increased expression of TLR4 and TNF-α mRNA/protein on PBMCs and increased serum sVCAM-1 is linked with reduced myocardial perfusion in DCM group. TLR4 and TNF-α may thus play a critical role in the myocardial perfusion inflammation injury in these patients.

Case-Control Studies ; Diabetic Cardiomyopathies ; blood ; Female ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Myocardium ; metabolism ; pathology ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo explore the effects of Sini Decoction (SD) on the expressions of Samd2 and Smad7 isoproterenol (Iso) induced myocardial fibrosis rats.

METHODSTotally 19 Wistar rats were randomly divided into 3 groups, i.e., the control group, the model group, and the SD group. Iso was injected to rats in the model group and the SD group, while normal saline was injected to rats in the control group. SD was given to rats in the SD group by gastrogavage, while normal saline was administered to rats in the control group and the model group by gastrogavage. Four weeks later Masson staining and electron microscopic analysis were performed in each group. The protein and mRNA expressions of Smad2 and Smad7 were detected using immunohistochemical assay and RT-PCR.

RESULTSMasson staining showed the IOD value of the myocardial collagen fiber was 9 303 in the model group, 2 459 in the SD group, and 4 224 in the control group, indicating the myocardial fibrosis was more obvious in the model group than in the SD group and the control group. The IOD value of Smad2 protein was 20 275 and the mRNA IOD of Smad2 protein was 0. 919 in the model group, while they were respectively 9 949 and 0. 561 in the SD group, indicating the protein and mRNA expressions of Smad2 were obviously higher in the model group than in the SD group (P < 0.05). The IOD value of Smad7 protein was 25 667 and the mRNA IOD of Smad7 protein was 0.222 in the model group, while they were respectively 93 147 and 0. 412 in the SD group, indicating the protein and mRNA expressions of Smad7 was obviously lower in the model group than in the SD group (P < 0.05).

CONCLUSIONSD could effectively inhibit Iso induced myocardial fibrosis, and its mechanism may be associated with down-regulating the expression of Smad2 and up-regulating the expression of Smad7.

Animals ; Cardiomyopathies ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Fibrosis ; Isoproterenol ; adverse effects ; Male ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Wistar ; Smad2 Protein ; metabolism ; Smad7 Protein ; metabolism

OBJECTIVETo investigate the association between cTnI phosphorylation/degradation and cardiomyopathies in extransplanted myocardium.

METHODScTnI phosphorylation and degradation as well as PKC (beta1, beta2) expressions were determined in extransplanted hearts from patients with cardiomyopathies (n = 8) and from traffic accidents (n = 6) by Western blot.

RESULTSThe cTnI bands were observed in LV myocardium of cardiomyopathy patients and normal myocardium while and cTnI degradation bands were only detected in LV myocardium from patients with cardiomyopathies. The phosphorylated cTnI bands were significantly upregulated in LV myocardium of cardiomyopathy patients compared to normal myocardium (P < 0.05). There was no myocardial PKCbeta1, PKCbeta2 expression in all examined hearts.

CONCLUSIONThe cTnI degradation products and increased phosphorylated cTnI expression are likely involved in the pathogenesis and development of cardiomyopathy.

Adult ; Cardiomyopathies ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Myocardium ; metabolism ; pathology ; Phosphorylation ; Protein Kinase C ; metabolism ; Protein Kinase C beta ; Signal Transduction ; Troponin I ; metabolism