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The purpose of this study was to explore whether dysglycemia, and/or an increased body mass index, and/or an increased waist/hip ratio increased the risk of hypertension in a lean population of South China. The association among dysglycemia, obesity, and hypertension has been well documented in Western populations. A stratified cluster sampling method was used according to the National Diabetes Mellitus Epidemiology Survey Program in 1998. Blood pressure, fasting plasma glucose, and plasma glucose were measured 2 hours after 75-g oral glucose consumption using the enzymatic method in the morning. Body height, weight, and waist and hip measurements were also collected for the survey. The criteria for the diagnosis of hypertension and diabetes mellitus, including impaired glucose tolerance (IGT), were those published by the World Health Organization in 1999. A total of 11,402 participants were included in the investigation (5,195 men and 6,207 women; age 20 to 74 years). A total of 1,775 cases of hypertension were confirmed in the survey. The prevalence of hypertension was significantly higher in those with diabetes mellitus than in those with a normal blood glucose level, in those with IGT than in those with normal glucose tolerance test findings, and in obese participants than in those with a normal weight (45.5% vs 14.4%, 32.2% vs 14.5%, and 20.6% vs 12.1%, respectively). Multiple logistic regression analysis indicated that age and gender-adjusted odds ratio of hypertension was 2.24 (95% confidence interval 1.88 to 2.68) with IGT compared with those without IGT. The odds ratio for hypertension associated with an increased body mass index and waist/hip ratio was 1.19 (95% confidence interval 1.17 to 1.21) and 1.08 (95% confidence interval 1.07 to 1.09), respectively. In conclusion, the data from an epidemiologic study in South China demonstrated that dysglycemia and increased body mass index and/or waist/hip ratio increase the risk of hypertension even in a lean Chinese population. [Copyright &y& Elsevier]

Abstract: Mesenchymal stem cells (MSCs) are attractive candidates for cell based therapies. However, the mechanisms responsible for stem cell migration and homing after transplantation remain unknown. It has been shown that insulin-like growth factor-1 (IGF-1) induces proliferation and migration of some cell types, but its effects on stem cells have not been investigated. We isolated and cultured MSC from rat bone marrow, and found that IGF-1 increased the expression levels of the chemokine receptor CXCR4 (receptor for stromal cell-derived factor-1, SDF-1). Moreover, IGF-1 markedly increased the migratory response of MSC to SDF-1. The IGF-1-induced increase in MSC migration in response to SDF-1 was attenuated by PI3 kinase inhibitor (LY294002 and wortmannin) but not by mitogen-activated protein/ERK kinase inhibitor PD98059. Our data indicate that IGF-1 increases MSC migratory responses via CXCR4 chemokine receptor signaling which is PI3/Akt dependent. These findings provide a new paradigm for biological effects of IGF-1 on MSC and have implications for the development of novel stem cell therapeutic strategies. [Copyright &y& Elsevier]

The cross-talk between cancer cells and monocyte-derived alveolar macrophages (Mo-AMs) promotes non-small cell lung carcinoma (NSCLC) progression. In this study, we report that both cancer cells and Mo-AMs robustly express beta 3-adrenergic receptor (ADRB3) in NSCLC. ADRB3 supports lung cancer cells proliferation and promotes chronic inflammation. Genetic and pharmacologic inhibition of ADRB3 reverses tumor growth and inflammation in mouse. Furthermore, we demonstrate that M5D1, a novel anti-ADRB3 monoclonal antibody, inhibits human lung cancer cells proliferation and inflammation via affecting the intracellular mTOR pathway and activating p53. In NSCLC patients, we confirmed that upregulation of ADRB3 expression correlates with tumor progression and poor prognosis. Altogether, these results shed light on the role of ADRB3 in NSCLC and suggest that M5D1 could become powerful antitumor weapons. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a fatal and currently incurable cardiopulmonary disease. Numerous microRNAs (miRNAs) serve important roles in the development of PAH. While the expression of miR-30a-5p was downregulated in the lung tissue of rats in a pulmonary hypertension rat model, the expression pattern and function of miR-30a-5p in human PAH remain unclear. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to examine miR-30a-5p and chitinase-3-like protein 1 (YKL-40) mRNA expression levels. The expression levels of YKL-40 and apoptosis-associated proteins were measured by western blot analysis. Cell proliferation assays and flow cytometry analysis were performed to examine cell proliferation and apoptosis, respectively. The association between miR-30a-5p and YKL-40 was determined by a luciferase reporter assay, RT-qPCR and western blot analysis. The relative expression levels of miR-30a-5p in plasma were increased in patients with PAH [median=13.23 (25th percentile=6.388, 75th percentile=21.91)] compared with normal controls [median=2.25 (25th percentile=1.4, 75th percentile=3.7). The expression of miR-30a-5p was significantly downregulated while the protein expression of YKL-40 was significantly upregulated in hypoxia-induced human pulmonary artery endothelial cells (HPAECs) when compared with the hypoxia-induced group at 0 h. miR-30a-5p overexpression promoted HPAEC growth and inhibited apoptosis of HPAECs under hypoxia. A miR-30a-5p mimic decreased the luciferase activity of a luciferase reporter construct containing YKL-40 3′-untranslated region and also decreased YKL-40 protein expression. YKL-40 overexpression partly alleviated the effects of miR-30a-5p upregulation on proliferation and apoptosis of HPAECs under hypoxia. In conclusion, the data indicated that miR-30a-5p promoted cell growth and inhibited apoptosis of HPAECs under hypoxia by targeting YKL-40. Therefore, the miR-30a-5p/YKL-40 axis may provide a potential target for the development of novel PAH therapies. [ABSTRACT FROM AUTHOR]

Abstract: Aim of this study: The panax notoginseng saponins (PNS) have been clinically used for the treatment of cardiovascular diseases and stroke in China. Evidences demonstrated that PNS could protect cardiomyocytes from injury induced by ischemia, but the underlying molecular mechanisms of this protective effect are still unclear. This study was aimed to investigate the protective effect and potential molecular mechanisms of PNS on apoptosis in H9c2 cells in vitro and rat myocardial ischemia injury model in vivo. Materials and methods: H9c2 cells subjected to serum, glucose and oxygen deprivation (SGOD) were used as in vitro models and SD rats subjected to left anterior descending (LAD) coronary artery ligation were used as in vivo models. The anti-apoptotic effect of PNS was evaluated by Annexin V/PI analysis or TUNEL assay. Mitochondrial membrane potential (Δψm) was detected by JC-1 analysis. The expression of Akt and phosphorylated Akt (p-Akt) were detected by western blot assay. Results: PNS exhibited anti-apoptotic effect both in H9c2 cells and in ischemic myocardial tissues. However, the effect was blocked in vitro by LY294002, a specific PI3K inhibitor. The anti-apoptotic effect of PNS was mediated by stabilizing Δψm in H9c2 cells. Furthermore the indices of the left ventricular ejection fractions (EF), left ventricular fractional shortening (FS), left ventricular dimensions at end diastole (LVDd) and left ventricular dimensions at end systole (LVDs) suggested that PNS improved rats cardiac function. PNS significantly increased p-Akt both in H9c2 cells and in ischemic myocardial tissues and this effect was also blocked by LY294002 in H9c2 cells. Conclusion: Results of this study suggested that PNS could protect myocardial cells from apoptosis induced by ischemia in both the in vitro and in vivo models through activating PI3K/Akt signaling pathway. [Copyright &y& Elsevier]

Abstract: Carvedilol is widely used in the treatment of cardiovascular diseases including atrial fibrillation. T-type Ca2+ channels have been recognized recently in the mechanisms underlying atrial arrhythmias. However, it is unclear whether carvedilol may affect the T-type Ca2+ channel. The present study evaluated the pharmacological effects of carvedilol on T-type calcium current (I Ca,T) in the murine HL-1 cell line. I Ca ,T was recorded by the whole-cell patch–clamp technique. Calcium transient was monitored by the fluorescent dye Fluo-4/AM and confocal laser scanning microscopy. Carvedilol reversibly inhibited I Ca ,T in a concentration-dependent manner, with an IC50 of 2.1µM. 3µM carvedilol was found to decrease the peak I Ca ,T amplitude at −20mV from 20.1±1.8pA/pF to 10.9±2.1pA/pF. Carvedilol significantly shifted the steady-state inactivation curve of I Ca ,T towards more negative potential by 12.8mV, while the activation curve was not significantly altered. Carvedilol delayed recovery from inactivation of I Ca ,T, time constant (τ) was 112.4±3.5ms in control and 270.1±4.7ms in carvedilol. Carvedilol-induced inhibition rate in I Ca ,T was enhanced with the increase in stimuli frequency, the inhibitory rate was 23.2±4.1% at 0.2Hz and 47.2±0.6% at 2Hz. Carvedilol still produced the significant decrease in the amplitude of I Ca ,T in the presence of H-89, PKA inhibitor. Carvedilol significantly inhibited the amplitude of the calcium transient in a concentration-dependent manner. These findings indicate that carvedilol inhibits I Ca ,T in atrial cells by mechanisms involving preferential interaction with the inactivated state of T-type Ca2+ channel. [Copyright &y& Elsevier]

Abstract: Heart attacks and congestive heart failure remain among the world''s most prominent health challenges despite the many breakthroughs. Bone marrow mesenchymal stem cells (BMSCs) have the potential to transdifferentiate into myocytes if an appropriate cardiac environment is provided. This study is meant to investigate the ability of BMSCs to differentiate into cardiomyocytes in a conditioned medium. BMSCs were isolated from rat femurs and tibias using Percoll gradient centrifugation method. Cells were expanded as undifferentiated cells in culture for more than 3 passages and their phenotypes were identified with flow cytometer. BMSCs were cocultured with neonatal rat ventricular myocytes in a rate of 1:10 separated by semipermeable membrane. BMSCs marker of CD29 were highly expressed (98.89±1.2%); however, CD34 could hardly be identified (5.61±0.1%). After coculturing with myocytes, some of BMSCs showed contraction which became more regular and more vigorous. As assessed by RT-PCR, SERCA2 and RyR2 were expressed by newly formed cells from 1 to 3 weeks. Immunostaining of newly differentiated BMSCs revealed positivity for cTnT. Some of these cells were positive for sarcomeric α-actinin, desmin, cTnT, and cTnI. Western blotting showed that cTnI protein expression was upregulated in these cells from 1 to 3 weeks. Newly formed BMSCs exhibited ultrastructural features of sarcomere formation and inward rectifier potassium current (I K1). It is concluded that BMSCs possess the potential to differentiate into cardiomyocytes in the cardiac environment. BMSCs provide an excellent model for development of stem cell therapeutics, and their potential in the cardiac repair under various pathological conditions. [Copyright &y& Elsevier]

Abstract: Carvedilol is a β- and α1-adrenoceptor antagonist. It is widely used in the treatment of cardiovascular diseases including atrial arrhythmias. However, it is unclear whether carvedilol may affect the repolarization currents, transient outward K+ current (I to) and ultra-rapid delayed rectifier K+ current (I Kur) in the human atrium. The present study evaluated effects of carvedilol on I to and I Kur in isolated human atrial myocytes by whole-cell patch-clamp recording technique. We found that carvedilol reversibly inhibited I to and I Kur in a concentration-dependent manner. Carvedilol (0.3 μM) suppressed I to from 9.2±0.5 pA/pF to 4.8±0.5 pA/pF (P <0.01) and I Kur from 3.6±0.5 pA/pF to 1.9±0.3 pA/pF (P <0.01) at +50 mV. I to was inhibited in a voltage-dependent manner, being significantly attenuated at test potentials from +10 to +50 mV, whereas the inhibition of I Kur was independent. The concentration giving a 50% inhibition was 0.50 μM for I to and 0.39 μM for I Kur. Voltage-dependence of activation, inactivation and time-dependent recovery from inactivation of I to were not altered by carvedilol. However, time to peak and time-dependent inactivation of I to were significantly accelerated, indicating an open channel blocking action. The findings indicate that carvedilol significantly inhibits the major repolarization K+ currents I to and I Kur in human atrial myocytes. [Copyright &y& Elsevier]

Background: The levels and trends of cardiovascular risk factors vary greatly throughout China. We examine 10-year trends of cardiovascular risk factors (1983-1994) and the factors related to these trends among low-risk cohorts of workers and farmers in Guangzhou, China.Methods: This is a cohort study of 3,131 workers and 3,493 farmers aged 25-64 years at baseline with 10 years of follow-up. We performed a longitudinal analysis to account for the aging of the cohorts and the repeated measures of the same individual.Results: At baseline the prevalence of overweight (including obese) ranged from 1.0% to 11.8%, hypertension ranged from 3.8% to 10.5%, and mean serum total cholesterol (TC) ranged from 155.4 mg/dl to 187.2 mg/dl. Although prevalence of smoking declined, blood pressure levels and body mass index (BMI) increased significantly, and lipid profiles changed unfavorably during the 10-year follow-ups. The prevalence of hypertension increased from 5.0 percentage points (female farmers) to 12.3 percentage points (male farmers). Mean TC increased significantly (e.g., +22.8 mg/dl and +17.0 mg/dl in male and female farmers, respectively). In the longitudinal data analyses, increase in BMI was associated with increase in blood pressure levels and TC. Significant adverse trends of risk factors persisted after adjustment for aging, education, BMI, smoking, and alcohol intake.Conclusion: Urgent action is needed to prevent and reverse the unhealthy trends occurring among these low risk Chinese workers and farmers. [ABSTRACT FROM AUTHOR]