Altered serum microRNAs as novel diagnostic biomarkers for atypical coronary artery disease.

BACKGROUND AND AIM: Atypical coronary artery disease (ACAD) is characterized by atypical angina pectoris or silent myocardial ischemia. However, conventional diagnostic techniques are insufficient to identify this subtype of coronary atherosclerotic pathology, and specific and sensitive markers for diagnosing ACAD are still currently lacking. The aim of the present study is to identify a novel serum microRNA (miRNA) expression profile of ACAD patients and evaluate its clinical diagnostic value. PATIENTS AND METHODS: 127 patients who were diagnosed with ACAD and 54 age-matched controls were enrolled in this study. An initial screen of miRNA expression was performed in serum samples from 35 patients and 20 controls using TaqMan Low Density Array. A stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and validation sets to confirm the levels of the altered miRNAs in 122 patients with ACAD and 68 controls. In addition, the potential target genes of the altered miRNAs were predicted using bioinformatics methods. RESULTS: The TaqMan low density array and RT-qPCR analysis identified four serum miRNAs including miR-487a, miR-502, miR-208 and miR-215 that were significantly increased, while one miRNA, miR-29b, that was significantly decreased in ACAD patients compared with normal controls (P<0.05). The area under the receiver-operating-characteristic (ROC) curve (AUC) for the combined 5 serum miRNAs were 0.850 (95% CI, 0.734-0.966, P<0.001) and 0.909 (95% CI, 0.858-0.960, P<0.001) for the training set and validation set, respectively. In addition, target gene prediction showed that these five altered miRNAs are involved in affecting various aspects of cardiac or vascular remodeling, especially in the pathway involving inflammation and fibrosis. CONCLUSION: Our findings indicate that the five altered serum miRNAs could be novel non-invasive biomarkers for ACAD and may also represent potential therapeutic targets for atherosclerosis and myocardial ischemia.

Oscillating high glucose enhances oxidative stress and apoptosis in human coronary artery endothelial cells.

PURPOSE: To investigate the toxic effect of oscillating high glucose (OHG) versus persistent high glucose (PHG) in inducing oxidative stress and cellular apoptosis in human coronary artery endothelial cells (HCAECs) in vitro. METHODS: HCAECs were incubated for 72 h continuously in normal glucose (5.5 mmol/L glucose), PHG (25 mmol/L glucose), OHG (5.5 mmol and 25 glucose mmol/L alternating every 6 h) and mannitol, respectively. Cellular viability, concentration of oxidative stress biomarkers (MDA and GSH) in the supernatants of cell culture, and intracellular ROS level were quantitated after exposure to different concentrations of glucose for a total 72 h. Apoptosis of HCAECs cultured with various glucose levels was evaluated by annexin V-FITC and PI staining followed by analysis with flow cytometry. The expressions of HO-1 and Nrf2 were measured by RT-qPCR and Western blotting at the end of the experiment. RESULTS: HCAECs cultured with PHG showed decreased cellular viability compared to those with normal level of glucose (p < 0.05). The decrease was more pronounced under OHG condition (p < 0.05). Cellular oxidative stress was provoked in HCAECs exposed to PHG with marked increased MDA level, reduced GSH concentration and elevated ROS production (p < 0.05). The stress was further amplified in the setting of OHG (p < 0.05). The cellular apoptosis was enhanced by culturing with PHG, and to a greater extent when incubated with OHG. Both expressions of HO-1 and Nrf2 were suppressed in HCAECs in persistent hyperglycemia condition, while the inhibition was more intense in the fluctuating hyperglycemia condition (p < 0.05). CONCLUSIONS: These findings indicate that OHG could be more detrimental to HCAECs than PHG. This is probably due to the enhancement of oxidative stress and cellular apoptosis induced by frequent glucose swings through the inhibition of Nrf2/HO-1 pathway.

MicroRNA expression profile in myocardial bridging patients.

BACKGROUND: Myocardial bridging (MB), a common benign coronary anomaly, may bring about some unwanted complications such as angina-like chest pain. The only way of MB detection is coronary arteriography or coronary computed tomographic angiography, which is costly and invasive. This study intended to profile a panel of circulating microRNAs (miRNAs) as potential biomarkers for the diagnosis of MB. METHODS: Using TaqMan Low-Density Array followed by quantitative reverse transcriptase PCR (qRT-PCR) validation, we analyzed the expression of miRNAs in serum samples from 90 MB patients and 50 non-MB controls. RESULTS: The Low-Density Array data showed that 196 miRNAs were differentially expressed in MB patient sera in comparison with controls. After qRT-PCR validation and receiver operating characteristic (ROC) analysis, a list of five miRNAs (miR-29b, miR-151-3p, miR-126, miR-503-3p and miR-645) showed the ability to distinguish MB patients from controls. The area under curve (AUC) values range from 0.722-0.938. CONCLUSIONS: We have demonstrated that this panel of five serum miRNAs is expected to become potential non-invasive biomarkers for detection of MB.

Xuezhikang attenuated the functional and morphological impairment of pancreatic islets in diabetic mice via the inhibition of oxidative stress.

Xuezhikang, purified from red yeast rice, is a traditional Chinese medicine with pleiotropic effects on the cardiovascular system. Oxidative stress plays a crucial role in the dysfunction of pancreas islet in diabetic condition and represents a promising therapeutical target for diabetes mellitus. Therefore, the purpose of this study was to explore the effects and possible mechanisms of xuezhikang on the microenvironment and insulin secretion by pancreatic islets in db/db diabetic mice. Our results showed that xuezhikang decreased the blood glucose level by improving glucose tolerance and insulin secretion in db/db mice. Xuezhikang protected islets from hyperglycemic injury as illustrated by the conserved ß-cell content and microenvironment. Furthermore, xuezhikang potently inhibited the expression of key factors in oxidative stress. In addition, administration of xuezhikang caused an upregulated expression of glucose-sensing apparatus. These observations provide evidence that the influence of xuezhikang on oxidative stress may at least partly account for its protective effects on the microenvironment and insulin secretion function of pancreatic islets in diabetes.

Acute myocardial infarction caused by tumor-associated thrombotic thrombocytopenic purpura: case report.

OBJECTIVE: To describe a case with acute myocardial infarction caused by gastric carcinoma-associated thrombotic thrombocytopenic purpura. CLINICAL PRESENTATION AND INTERVENTION: A 79-year-old man was admitted with abdominal pain and pyrexia. He later developed cardiac complications and microangiopathy that indicated worsening progression. Manifold evidence confirmed the diagnosis of myocardial infarction caused by thrombotic thrombocytopenic purpura. The patient was treated mainly with plasma transfusion incorporated with steroids. CONCLUSION: This case should remind physicians to consider microangiopathy as a differential diagnosis in patients with unexplained cardiac symptoms or atypical presentation. Early diagnosis and treatment are helpful in decreasing the sequelae of this syndrome.

Potential mechanism for endothelial progenitor cell therapy in acute myocardial infarction: Activation of VEGF- PI3K/Akte-NOS pathway.

Mounting evidence suggests that transplanting endothelial progenitor cells (EPCs) into the myocardium improves cardiac function after myocardial infarction (MI). However, the mechanism remains controversial. The aim of this study was to investigate the role played by the VEGF- PI3K/Akt-eNOS pathway in EPC-based cell therapy. Cultured EPCs, which were identified by morphology, function, and cell surface markers, were transplanted into the border zone after left anterior descending coronary artery ligation in mice. Expression levels of VEGF, p-Akt, and eNOS in the border zone were elevated three days after EPC transplantation. EPC therapy enhanced expression of VEGFR-2, increased microvessel density, and reduced interstitial fibrosis in the border zone after MI. The left ventricular fractional shortening was increased and the left ventricular diameter was smaller after EPC treatment. Wortmannin inhibited the expression of p-Akt and was associated with decreased cardiac function. Our study suggests that EPC transplantation improves cardiac function after MI, mediated at least partially by activation of the VEGF -PI3K/Akt-eNOS pathway.

Association of pericardial adipose tissue volume with presence and severity of coronary atherosclerosis.

PURPOSE: This study was to investigate whether high pericardial adipose tissue (PAT) volume is related to the presence and severity of coronary artery disease (CAD). METHODS: Consecutive patients (310 patients) who underwent both dual-source 64-slice CT and percutaneous coronary angiography were recruited into this study. Waist circumference (WC), body mass index (BMI), blood biochemical variables, coronary artery calcium (CAC) score and Gensini score were measured. Pericardial adipose tissue (PAT) volume was determined by dual-source CT. RESULTS: PAT volume was positively correlated with BMI, WC, gender (male), hypertension, diabetes, age, total cholesterol and low-density lipoprotein-cholesterol. PAT volume in CAD patients was significantly higher than that in patients without CAD (238.36 ± 81.21 cm3 vs. 200.13±72.34 cm3). PAT volumes in patients with multi-vessel lesions were significantly higher than those with one-vessel lesions (P < 0.001). A significant correlation between PAT volume and CAC score (r=0.305, P < 0.001) was found. PAT volume was an independent factor affecting Gensini score. CONCLUSION: PAT volume was significantly correlated with traditional cardiovascular risk factors, the severity of coronary atherosclerosis and the number of stenotic coronary vessels. Thus, PAT volume may be a reliable marker to evaluate the presence and severity of CAD.

Periodic vs constant high glucose in inducing pro-inflammatory cytokine expression in human coronary artery endothelial cells.

OBJECTIVE AND DESIGN: Fluctuating hyperglycemia exerts a more deleterious effect than constant hyperglycemia on cardiovascular outcome in diabetic patients. We investigated the inflammatory responses of human coronary artery endothelial cells (HCAECs) to constant and periodic high glucose in vitro. MATERIAL AND TREATMENT: HCAECs were incubated for 72 h continuously either in normal glucose (5.5 mmol/L), constant high glucose (25 mmol/L glucose), periodic high glucose (5.5 and 25 mmol/L glucose alternating every 6 h) or mannitol. METHODS: Concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-α and intercellular adhesion molecule (ICAM)-1 in the supernatants of cell culture were measured using ELISA kits. The mRNAs of IL-6, TNF-α and ICAM-1 were evaluated by real-time quantitative PCR. RESULTS: Periodic high glucose caused a more intense inflammatory response than normal glucose and constant high glucose in HCAECs, with a marked increase in IL-6, TNF-α and ICAM-1 in supernatants of cell culture (P < 0.05). The concentrations of the three pro-inflammatory cytokine mRNAs were higher in cells exposed to periodic high glucose than those exposed to constant high glucose and normal glucose (P < 0.05). CONCLUSION: In cultured HCAECs, periodic high glucose evoked a more intense inflammatory response than constant high glucose.

Effect of ezetimibe on insulin secretion in db/db diabetic mice.

OBJECTIVE: To investigate the effect of ezetimibe on the insulin secretion in db/db mice. METHODS: The db/db diabetic mice aged 8 weeks were randomly assigned into 2 groups and intragastrically treated with ezetimibe or placebo for 6 weeks. The age matched db/m mice served as controls. At the end of experiment, glucose tolerance test was performed and then the pancreas was collected for immunohistochemistry. In addition, in vitro perfusion of pancreatic islets was employed for the detection of insulin secretion in the first phase. RESULTS: In the ezetimibe group, the fasting blood glucose was markedly reduced, and the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly lowered when compared with those in the control group (P < 0.05). At 120 min after glucose tolerance test, the area under curve in the ezetimibe group was significantly smaller than that in the control group (P < 0.05), but the AUC(INS0-30) was markedly higher. In vitro perfusion of pancreatic islets revealed the first phase insulin secretion was improved. In addition, the insulin expression in the pancreas in the ezetimibe group was significantly increased as compared to the control group. CONCLUSION: Ezetimibe can improve glucose tolerance, recover the first phase insulin secretion, and protect the function of ß cells in mice.

Reversible cardiogenic shock caused by atrioventricular junctional rhythm after percutaneous coronary intervention.

An 82-year-old female patient undergoing cardiogenic shock caused by atrioventricular junctional rhythm immediately after percutaneous coronary intervention (PCI) is described. Pharmacotherapy was invalid, and subsequent application of atrial pacing reversed the cardiogenic shock. PCI-related injury of sinuatrial nodal artery leading to acute atrial contractility loss, accompanied by atrioventricular junctional arrhythmia, was diagnosed. We recommend that preoperative risk evaluation be required for multi-risk patients. Likewise, emergent measures should to be established in advance. This case reminds us that atrial pacing can be an optimal management technique once cardiogenic shock has occurred.

Glucose metabolism in outpatients with new-onset hypertension in Chinese Han population.

The aim of this study was to assess the prevalence of glucose abnormalities in a Chinese Han population with untreated new-onset hypertension. Four hundred and ninety-nine new-onset hypertensive patients without diabetes were enrolled in this study. An abnormal glucose metabolism was diagnosed in 57.1% of the new-onset hypertensive patients without previously diagnosed diabetes. Stratified by age, the prevalence of diabetes and prediabetes were increased with aging. Male sex, advanced age, higher serum triglycerides, and homeostasis model assessment of insulin resistance levels were all significantly associated with the increased risks of pre-diabetes or diabetes in new-onset hypertensive patients when analyzed by the logistic regression analysis.

Erythropoietin improves the efficiency of endothelial progenitor cell therapy after myocardial infarction in mice: effects on transplanted cell survival and autologous endothelial progenitor cell mobilization.

BACKGROUND: Endothelial progenitor cells (EPCs) participate in vascular repair and angiogenesis. Thus, EPC transplantation into ischemic myocardium might improve cardiac function; however, the vast majority of cells die within a short period. The present study was designed to investigate whether exogenous erythropoietin (EPO) delivery could improve the survival of transplanted EPCs and enhance the efficiency of EPC-based cell therapy. METHODS: Myocardial infarction was induced in wild-type mice by ligating the left anterior descending coronary artery. Enhanced green fluorescent protein-EPCs with or without EPO were transplanted into peri-infarct myocardium. Enhanced green fluorescent protein-EPCs were detected 7 and 28 d after surgery. The amount of circulating EPCs was analyzed 3 and 28 d after surgery. The stromal cell-derived factor-1α and vascular endothelial growth factor concentrations, microvessel density, apoptosis, fibrosis in the peri-infarct myocardium, and cardiac function were compared among the groups. RESULTS: More enhanced green fluorescent protein-EPCs were found in the hearts treated with EPC + EPO than in those treated with EPC alone. The circulating EPC level was markedly elevated after EPC + EPO treatment compared with EPC application alone. Stromal cell-derived factor-1α and vascular endothelial growth factor were increased accordingly, along with increased microvessel density, decreased apoptosis, and reduced fibrosis in the peri-infarct myocardium. Left ventricular fractional shortening was greater and the interventricular septum was thicker after EPC + EPO treatment compared with EPC treatment alone. CONCLUSIONS: EPO improved the efficiency of EPC therapy in mice with myocardial infarction. This effect was associated with enhanced transplanted EPC survival and autologous EPC mobilization.

Protective effect of ligustrazine against myocardial ischaemia reperfusion in rats: the role of endothelial nitric oxide synthase.

1. The aim of the present study was to determine whether ligustrazine (2,3,5,6-tetramethylpyrazine; TMP) exerts a cardioprotective effect during myocardial ischaemia reperfusion (IR), and to investigate the underlying mechanisms and the role of endothelial nitric oxide synthase (eNOS) in cardioprotection. 2. Sprague-Dawley rats were divided into a sham group and five IR groups: IR control, TMP pretreated, TMP + wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor), N(G) -nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) and TMP + L-NAME. IR was produced by 35 min of regional ischaemia followed by 120 min of reperfusion. Myocardial infarct size, oxidative stress, myocardial apoptosis, nitric oxide (NO) production, and expression of phosphorylated protein kinase B (Akt) and eNOS were measured. 3. TMP markedly decreased infarct size and attenuated myocardial apoptosis, as evidenced by a decrease in the apoptotic index and reduced caspase-3 activity. TMP treatment caused a marked increase in NO production. Cotreatment with wortmannin or L-NAME completely blocked the TMP-induced NO increase. TMP induced phosphorylation of Akt at Ser 473 (1.61 ± 0.18 vs 0.79 ± 0.10 in the IR control group) and phosphorylation of eNOS at Ser1177 (1.87 ± 0.33 vs 0.94 ± 0.22 in the IR control group). Wortmannin abrogated the phosphorylation of Akt and eNOS induced by TMP. 4. These data suggest that ligustrazine has anti-apoptotic and cardioprotective effects against myocardial IR injury and that it acts through the PI3K/Akt pathway. In addition, the phosphorylation of eNOS with subsequent NO production was found to be an important downstream effector that contributes significantly to the cardioprotective effect of TMP.

[Effect of depside salt from salvia miltiorrhizae in repairing advanced glycation end products-induced late endothelial progenitor cell dysfunction and its molecular mechanism].

OBJECTIVE: To investigate the effects of depside salt from salvia miltiorrhizae (DSSM) in repairing advanced glycation end products (AGE)-induced late endothelial progenitor cell (EPC) dysfunction, and its possible molecular mechanism. METHODS: Mononuclear cells (MNCs) were separated using density gradient centrifugation from human umbilical cord blood, and cultured with EGM-2-MV culture fluid to late EPCs. Then the EPCs were divided into 5 groups: Group A incubated with 200 microg/mL AGE-modified bovine serum albumin (AGE-albumin) alone (A), Groups B, C and D with equal dosage of AGE-albumin plus DSSM at different dosages (0.1 microg/mL, 1 microg/mL, and 10 microg/mL), Group E with 200 microg/mL of unmodified-AGE. The late EPCs apoptosis was detected by Annexin V+/PI double-stain, angiogenic capacity was detected by ECMatrix-gel, mRNA expressions of the receptor for AGE (RAGE) and endothelial nitric oxide synthase (eNOS) were measured by reverse-transcriptase polymerase chain reaction (RT-PCR), and the protein expressions of RAGE, eNOS and protein kinase (Akt) were measured by Western blot. RESULTS: Compared with Group E, in Group A, the Annexin V+/PI- ratio and expression of RAGE in EPCs increased, the angiogenic capacity, mRNA and protein expressions of eNOS, and protein expression of Akt decreased significantly. These abnormal changes in Groups C and D were significantly smaller than those in Group A (P < 0.05 or P < 0.01). And all the indices in Group D were adjacent to those in Group E, showing insignificant difference between the two groups (P > 0.05). CONCLUSIONS: AGE could injure the function of EPCs, revealing increase of cell apoptosis and migration, deprivation of angiogenic capacity in vitro. DSSM could repair the EPCs dysfunction induced by AGE-albumin. Up-regulation of eNOS and Akt in these cells may be involved in the mechanism.

Diagnostic accuracy of dual-source CT coronary angiography: The effect of average heart rate, heart rate variability, and calcium score in a clinical perspective.

BACKGROUND: Dual-source CT coronary angiography (CTCA) has been used to detect coronary artery disease; however, the factors with potential to affect its diagnostic accuracy remain to be defined. PURPOSE: To prospectively evaluate the accuracy of dual-source CTCA in diagnosing coronary artery stenosis according to conventional coronary angiography (CAG), and the effect of average heart rate, heart rate variability, and calcium score on the accuracy of CTCA. MATERIAL AND METHODS: A total of 113 patients underwent both dual-source CTCA and CAG. The results were used to evaluate the findings in dual-source CTCA to assess the accuracy in the diagnosis of > or =50% (significant stenosis) and >75% (severe stenosis) of coronary artery according to those by CAG. Patients were divided into subgroups according to their heart rate (HR), HR variability (HRV), and calcium score, and the accuracy of CTCA was further evaluated. The chi-square test was used to analyze the difference in sensitivity and specificity for the detection of > or =50% and >75% coronary stenosis among subgroups. The generalized estimation equation method was used in per-vessel analysis to adjust for within-patient correlation. RESULTS: In all, 113 patients had 338 vessels and 1661 segments evaluated by CAG. Dual-source CTCA displayed 1527 segments (91.9%). Among them, 1468 segments (calcium score by CAG score 1, n=1018; score 2, n=270; score 3, n=180) were assessable in CTCA. On a per-patient analysis, the sensitivity and specificity of CTCA were 93.9% and 93.5% for significant stenosis and 86.9% and 98.1% for severe stenosis. On a per-vessel basis, the sensitivity and specificity were 90.2% and 97.1% for significant and 83.3% and 98.1% for severe stenosis. On a per-segment analysis, the sensitivity and specificity were 90.2% and 97.1% for significant and 83.3% and 98.1% for severe stenosis. Average HR had no effect on the sensitivity and specificity of CTCA (P>0.05); whereas HRV and calcium score had some effect on the sensitivity and specificity of CTCA (P<0.05). CONCLUSION: On a per-patient, per-vessel, and per-segment basis, dual-source CTCA has a high sensitivity and specificity for the diagnosis of coronary artery stenosis. Average HR has no effect on the diagnostic accuracy of CTCA, while HRV and calcium score have a statistically significant effect on the sensitivity and specificity of CTCA.

[Membrane testosterone receptors in cultured vascular smooth muscle cells].

OBJECTIVE: To determine the presence of membrane testosterone receptors in cultured vascular smooth muscle cells (VSMC), and investigate their relationship with classical intracellular androgen receptors (iAR). METHODS: VSMCs were cultured from the thoracic aorta of male Sprague-Dawley rats by the explant method. Subconfluent VSMCs were incubated with serum-free medium for 24 h to obtain quiescent non-dividing cells, and then treated with the indicated agents. The aliquots of VSMCs were labeled with testosterone-BSA-FITC (T-BSA-FITC) and analyzed by flow cytometry. Classical iARs in intact- and permeabilized-cells were detected with anti-iAR antibodies and FITC-labeled secondary antibodies by immunofluorescence, followed by flow cytometry analysis. RESULTS: Incubation of VSMCs with T-BSA-FITC obviously increased their relative fluorescence intensity at 10 sec as compared with the untreated controls (P < 0.01), and so did it at 10 min in comparison with the treatment with BSA-FITC alone or together with free testosterone (P < 0.01). Pretreatment with iAR antagonist flutamide exhibited no significant influence on the relative fluorescence intensity of VSMCs (P = 0.318). Traditional iARs were not detectable on the surface of intact VSMCs, although permeabilized cells contained iARs. CONCLUSION: VSMCs contain testosterone receptors in the plasma membrane, and these membrane receptors are not identical to classical iARs.

[Testosterone at physiological level inhibits PGF2alpha-induced increase in intracellular Ca2+ in cultured vascular smooth muscle cells].

OBJECTIVE: To explore the acute effects of testosterone at the physiological level on PGF2alpha-induced increase in intracellular Ca2+ in cultured vascular smooth muscle cells (VSMCs). METHODS: VSMCs from the thoracic aorta of male Sprague-Dawley rats were cultured using the explant method. The subconfluent VSMCs were incubated with serum-free medium for 24 hours to obtain quiescent non-dividing cells and then treated with the indicated agents. For the measurement of [Ca2+]i, the VSMCs were loaded with fura-2. Changes of [Ca2+]i were determined ratiometrically with a Nikon TE-2000E system. RESULTS: The resting level of [Ca2+]i was around 100 nmol/L in the VSMCs. Exposing cells to perfusate containing 10 micromol/L PGF2alpha triggered an immediate and transient peak in [Ca2+]i, which gradually decreased afterwards. Interference at the peak with the physiological concentration (40 nmol/L) of testosterone significantly decreased the peak-to-baseline time of [Ca2+]i, compared with ethanol vehicle (104.9 +/- 27.0 s vs 153.5 +/- 40.4 s, P < 0.01). Pretreatment with testosterone at 40 nmol/L for 2 minutes also reduced the peak-to-baseline time of [Ca2+]i significantly in comparison with the ethanol control (120.6 +/- 32.0 s vs 151.4 +/- 27.4 s, P < 0.01), but it had no significant effect on the peak level of PGF2alpha-induced intracellular Ca2+ (390.0 +/- 126.0 nmol/L vs 403.4 +/- 160.7 nmol/L, P > 0.05). CONCLUSION: Testosterone at physiological concentration inhibits PGF2alpha-induced Ca2+ fluxes, probably via receptor-operated calcium channels by a non-genomic mechanism in VSMCs, which may be involved in the vasodilatory effect of testosterone.

[Testosterone therapy improves cardiac function of male rats with right heart failure].

OBJECTIVE: Clinical studies have shown decreased levels of sexual hormones, particularly testosterone deficiency, in men with chronic heart failure (CHF). The authors aimed to investigate the effect of testosterone on cardiac function and the possible mechanism of androgen protecting the heart in male rats. METHODS: Forty-three male SD rats were randomly divided into 3 groups: right heart failure (RHF, n = 15), physiologic testosterone treatment (TT, n = 15) and control (n = 13). The RHF group was given intraperitoneal injection of monocrotaline at 60 mg/kg to make RHF models; the TT group was injected with testosterone at 5 mg/kg 3 days after monocrotaline administration; and the control group received equal volume of saline. The CD34+ cells in the peripheral blood of each rat were counted by flow cytometry. The levels of serum testosterone and tumor necrosis factor alpha (TNF-alpha) were measured by chemiluminescence immunoassay and enzyme linked immunosorbent assay, respectively. The hearts, lungs and livers of all the surviving rats were excised at 6 weeks for pathological and immunohistochemical examinations. RESULTS: The level of serum testosterone was gradually decreased, while that of TNF-alpha obviously increased in the RHF group. After testosterone treatment, the TT group showed a remarkable improvement of cardiac performance and a significant decrease in the level of serum TNF-alpha as compared with the RHF group. Statistically significant differences were observed neither in the CD34+ cell count in the peripheral blood nor in the CD34+ expression of the myocardial cells between the TT and RHF groups. CONCLUSION: Physiological supplementation of testosterone can improve the cardiac function of RHF male rats, probably through its inhibition of TNF-alpha rather than by autologous mobilization of bone marrow stem cells.

Racial differences in coronary artery lesions: a comparison of coronary artery lesions between mainland Chinese and Australian patients.

AIMS: The purpose of this study was to compare coronary lesions in mainland Chinese and Australians using coronary angiography (CAG). METHODS AND RESULTS: 6251 suspected coronary heart disease (CHD) patients (3021 Chinese patients from Nanjing and 3230 Australian patients from Sydney) who underwent a CAG between January 1, 2001, and December 31, 2003, were studied. Of these, 69.4% Chinese and 75.5% Australians were diagnosed with CHD. The incidences of both left main coronary artery (LM) and left anterior descending branch (LAD) lesions in Australians were higher than that for Chinese of the same gender. In the same age range, above 40, Gensini scores of Australians were significantly higher than those of Chinese. CONCLUSION: In both Chinese and Australians, men had more severe coronary lesions than women. Comparison among different age ranges in the 2 ethnic groups shows that Australians typically have artery lesions more than 10 years earlier than mainland Chinese.