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.

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.

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.

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.

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.

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.

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.

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.

[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.

[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 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.

[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.

Apoptosis and expression of uncoupling protein-2 in pressure overload-induced left ventricular hypertrophy.

OBJECTIVE: To explore the possible role of uncoupling protein-2 (UCP2) in cardiomyocyte apoptosis in pressure overload-induced left ventricular hypertrophy (LVH). METHODS AND RESULTS: Pressure overload was developed in 21 Sprague-Dawley rats by thoracic aortic constriction at 12 weeks of age. An equal number of sham-operated, age-matched rats served as controls. Aortic blood pressure (ABP), LVH, myocardial apoptosis index (MAI), and UCP2 mRNA expression were quantified in 7 subgroups of 3 treated and 3 control rats that were killed, at 1, 2, 4, 7, 14, 21, or 30 days post-surgery, respectively,. Compared to controls, ABP increased gradually throughout the study in the treated rats; LVH did not develop significantly until 4 days after surgery and increased progressively afterwards. The MAI increased immediately after surgery, reached a plateau from 4 to 7 days, and then declined rapidly; apoptosis was undetectable throughout the study in the cardiomyocytes of the control rats. In treated rats, the expression of UCP2 mRNA in myocardium was upregulated at 4 days, and developed progressively to the end of the experiment. CONCLUSIONS: (i) Apoptosis of cardiomyocytes is an important regulatory mechanism that is involved in the cardiac adaptive response to pressure overload, and (ii) the apoptosis of cardiomyocytes may be suppressed, in part, by UCP2.

[Coronary artery lesion comparison between Chinese and Australian patients with coronary artery disease].

OBJECTIVE: To compare coronary lesion characteristics by coronary angiography (CAG) between yellows and whites. METHODS: CAG results of 3021 Chinese patients, defined as yellows, from Nanjing and 3230 Australian patients, defined as whites, from Sydney were analyzed. The coronary artery lesion was evaluated by the number and location of coronary lesion and Gensini scores. RESULTS: (1) Coronary stenosis was diagnosed in 69.4% Chinese patients and 75.5% in Australians. The involved coronary arteries were left anterior descending branch, right coronary artery, left circumflex branch and left main coronary artery in a descending order in both Chinese and Australians. (2) The incidences of three-vessel disease and left main disease of yellows were significantly lower than that of whites in both male (29.8% vs. 34.0% and 9.6% vs. 14.2%) and female patients (15.8% vs. 26.2% and 4.9% vs. 11.6%) respectively, all P < 0.05. (3) There was an age-dependent Gensini scores increase in both yellows and whites patients and Gensini scores at age 40 and more of whites were significantly higher than those of yellows in comparable age groups. CONCLUSION: The incidences of three-vessel disease and left main disease as well as Gensini score were significantly higher in Australian patients than those of Chinese patients.

Apoptosis in pressure overload-induced cardiac hypertrophy is mediated, in part, by adenine nucleotide translocator-1.

This study explored the role of adenine nucleotide translocator-1 (ANT1) in cardiomyocyte apoptosis during left ventricular hypertrophy (LVH) that developed in response to pressure overload. Pressure overload was induced surgically in 21 male Sprague-Dawley rats by thoracic aortic constriction at 12 weeks of age. An equal number of sham-operated, age-matched male rats served as controls. Aortic blood pressure (ABP), LVH, myocardial apoptosis index (MAI), and ANT1 mRNA expression were quantified in 7 subgroups of 3 treated and 3 control rats that were killed, respectively, at 1, 2, 4, 7, 14, 21, or 30 days post-surgery. Compared to controls, ABP increased gradually throughout the study in the treated rats with aortic coarctation; LVH did not develop significantly until 4 days post-surgery and increased progressively afterwards. The myocardial apoptosis index (assayed by TUNEL-labeling) increased immediately post-surgery, reached a plateau from 4 to 7 days, and then declined rapidly; apoptosis was undetectable throughout the study in cardiomyocytes of control rats. In treated rats, the expression of ANT1 mRNA in myocardium was up-regulated at 4 days, peaked at 7 days, and returned to control levels at 14 days post-surgery. These findings suggest that (i) apoptosis of cardiomyocytes is an important regulatory mechanism that is involved in the cardiac adaptive response to pressure overload, and (ii) the apoptosis of cardiomyocytes is mediated, in part, by ANT1.

[Efficacy of adaptive pressure support servo-ventilation in patients with congestive heart failure and Cheyne-Stokes respiration].

OBJECTIVE: To investigate the efficacy of adaptive pressure support servo-ventilation (APSSV) on Cheyne-Stokes respiration (CSR) in congestive heart failure (CHF). METHODS: 14 patients with CHF and CSR were recruited. During sleep, oxygen therapy and APSSV were separately performed. Comparison before and after each treatment was made for the following items: a) parameters of sleep respiration, sleep structure and quality; b) cardiac function index such as left ventricle ejection fraction (LVEF) and 6 minutes' walking distance; c) plasma endothelin-1 (ET-1) levels. RESULTS: Compared with the baseline level before treatment, the apnea hypopnea index significantly decreased during oxygen therapy (P < 0.05) and further declined during APSSV (P < 0.01); on the contrary, the lowest pulse oxygen saturation increased during oxygen therapy (P < 0.05) and further elevated during APSSV (P < 0.01). Compared with arousal index before treatment, it was significantly lower during oxygen therapy (P < 0.05) and the lowest during APSSV (P < 0.01). Compared with both during oxygen therapy and before treatment, during APSSV the percentage ofI + II stage sleep time/total sleep time was significantly lower while the percentage of III + IV stage sleep time/total sleep time was significantly higher. The above percentages during oxygen therapy and before treatment showed no significant difference (P < 0.05). LVEF was significantly higher during APSSV than during oxygen therapy and before treatment (P < 0.05). Six minutes' walking distance was the shortest before treatment and the longest during APSSV. There was a significant difference among that before treatment, during oxygen therapy and APSSV (all P < 0.01). The plasma ET-1 level showed significantly lower during APSSV than that before and during oxygen treatment (P < 0.05), but no significant difference between the levels before and during oxygen treatment (P > 0.05). CONCLUSION: APSSV, more effective than oxygen therapy, is of great clinical significance in improvement of CHF and its prognosis by a better sleep and breathing.

[Expression of Toll-like receptor 2/4 mRNA in myocardium in mice with hemorrhagic shock].

OBJECTIVE: To investigate the effect of hemorrhagic shock without resuscitation on expression of Toll-like receptor (TLR) in myocardium of rats and its significance. METHODS: Forty-five C57BL/6 mice were randomly divided into 3 groups: hemorrhagic group, sham operation group and lipopolysaccharide (LPS) group, with 15 mice in each group. The hemorrhagic shock mouse model was reproduced by heart puncture. Expression levels of TLR2 mRNA and TLR4 mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR). Left ventricular end-systolic pressure (LVESP) was determined and adopted as an index of left ventricle contractile function. RESULTS: (1)Both hemorrhagic shock and LPS challenge led to a reduction in arterial blood pressure in mice when compared with sham operation group. Both hemorrhagic shock and LPS challenge could result in left ventricle contractile dysfunction when compared with sham operation group. (2)Expression levels for TLR2 and TLR4 genes were upregulated in myocardium to various extents after hemorrhagic shock and LPS challenge, while in contrast the changes were absent in sham operation group. CONCLUSION: (1)The up-regulation of TLR2 and TLR4 genes is closely related with hemorrhagic shock and LPS-induced left ventricle contractile dysfunction, and there may exist a difference in signal transduction pathway between the two pathological conditions. (2)The host ability of innate immune response may be reinforced by the up-regulation of TLR2 and TLR4, whereas overexpression of them may also impair the function of tissues or organs.

[Regulation of androgen receptor mRNA expression by testosterone in cultured vascular smooth muscle cells].

OBJECTIVE: To investigate the effects of testosterone exposure on androgen receptor (AR) mRNA expression in cultured vascular smooth muscle cells (VSMCs). METHODS: VSMCs were cultured from the thoracic aorta of male SD rats using explant method. The total RNA was extracted by one-step guanidine isothiocyanate method and subjected to Northern blotting analysis for determining AR mRNA level. The effect of testosterone on the viability and growth of VSMCs were studied by means of cell counting and tritiated thymidine incorporation assay. RESULTS: Testosterone treatment of the synchronized VSMCs for 24 h increased intracellular AR mRNA expression in a dose-dependent manner, with relative mRNA level of 97.67+/-7.22, 98.00+/-13.58, 143.33+/-10.99, 177.67+/-14.62 and 185.67+/-19.97 corresponding to testosterone doses of 0, 4 nmol/L, 40 nmol/L, 400 nmol/L and 4 micromol/L, respectively. Incubation of synchronized VSMCs with testosterone at a physiological level of 40 nmol/L for 24 h resulted in a mean of 30% up-regulation of AR mRNA level, compared with that of untreated cells. During AR up-regulation, testosterone had no significant effects on the cell number and DNA synthesis of VSMCs as measured by cell counting and tritiated thymidine incorporation assay. CONCLUSION: Self-initiated up-regulation of AR mRNA expression occurs in synchronized VSMCs, which is independent of testosterone that influences apoptosis or growth rate of the cells, suggesting the involvement of AR in androgen regulational at the transcription level in VSMCs.