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TWIST1 is an important basic helix‐loop‐helix protein linked to multiple physiological and pathological processes. Although TWIST1 is believed to be involved in vascular pathogenesis, its effects on homeostasis of smooth muscle cells (SMCs) remain poorly understood. Here, we show that TWIST1 protein levels were significantly elevated during SMC phenotypic switching in vivo and in vitro. TWIST1 overexpression promoted phenotypic switching of SMCs, while siRNA targeting of TWIST1 prevented cell transition. Mechanistically, TWIST1 decreased the level of microRNA‐143/145, which governs smooth muscle marker gene transcription. In addition, TWIST1 repressed p68 mRNA and protein expression, a crucial modulator of SMC behavior and microRNA biogenesis. Our co‐immunoprecipitation assay demonstrated a previously unrecognized molecular interaction between TWIST1 and p68 protein. Finally, we found that TWIST1 triggered SMC phenotypic switching and suppressed microRNA‐143/145 expression by promoting the proteasomal degradation of p68. These data suggest a novel role of TWIST1 in the regulation of SMC homeostasis by modulating p68/microRNA‐143/145 axis., Increased TWIST1 expression leads to the suppression of the DDX5/microRNA‐143/145 pathway in VSMC, which induces phenotypic switching of VSMC and promotes the progression of vascular remodeling. Therefore, TWIST1 might be a attractive therapeutic target for inhibiting phenotype‐related vascular disorders.

Growing evidence has shown that apelin/APJ system functions as a critical mediator of cardiac development as well as cardiovascular function. Here, we investigated the role of apelin in the cardiomyogenic differentiation of mesenchymal stem cells derived from Wharton's jelly of human umbilical cord in vitro. In this research, we used RNA interference methodology and gene transfection technique to regulate the expression of apelin in Wharton's jelly-derived mesenchymal stem cells and induced cells with a effective cardiac differentiation protocol including 5-azacytidine and bFGF. Four weeks after induction, induced cells assumed a stick-like morphology and myotube-like structures except apelin-silenced cells and the control group. The silencing expression of apelin in Wharton's jelly-derived mesenchymal stem cells decreased the expression of several critical cardiac progenitor transcription factors (Mesp1, Mef2c, NKX2.5) and cardiac phenotypes (cardiac α-actin, β-MHC, cTnT, and connexin-43). Meanwhile, endogenous compensation of apelin contributed to differentiating into cells with characteristics of cardiomyocytes in vitro. Further experiment showed that exogenous apelin peptide rescued the cardiomyogenic differentiation of apelin-silenced mesenchymal stem cells in the early stage (1-4 days) of induction. Remarkably, our experiment indicated that apelin up-regulated cardiac specific genes in Wharton's jelly-derived mesenchymal stem cells via activating extracellular signal-regulated kinase (ERK) 1/2 and 5.

Recent studies have indicated that stem cell implantation increases cardiac function by repairing damaged myocardium. We investigated whether intracoronary transplantation of autologous bone marrow-derived mononuclear cells (BMMCs) confers beneficial effects in patients with refractory chronic heart failure. Twenty-eight patients received standard heart failure medication and BMMC transplantation (BMMC treatment) or standard medication only (controls). BMMCs were harvested from each patient. Clinical manifestations, biochemical assays, rhythm studies, echocardiograms, and positron emission tomograms were recorded. Fourteen patients with cell grafting had symptomatic relief of heart failure within 3 days. Left ventricular ejection fraction increased by 9.2% and 10.5% at 1 week and 3 months after the procedure, respectively, versus baseline (p0.01 for the 2 comparisons). Left ventricular end-systolic volume decreased by 30.7% after 3 months (p0.01). Brain natriuretic peptide levels at days 3 and 7 after cell infusion significantly decreased by 69.2% and 70.4%, respectively, whereas atrial natriuretic peptide levels increased by 30.1% at day 7. Positron emission tomographic analysis showed a significant increase in cell viability of 10.3% in the infarcted zone. No patient died in the BMMC-treated group at 6-month follow-up. In contrast, heart failure did not improve in any control patient. Left ventricular ejection fraction decreased by 7.2% after 3 months. Two control patients died from heart failure within 6 months. In conclusion, this is the first demonstration in humans that intracoronary BMMC transplantation is a feasible and safe therapeutic strategy to decrease symptoms, increase cardiac function, and possibly prolong life in patients with end-stage heart failure refractory to standard medical therapy.

Background and Purpose— It is still controversial whether elevated plasma homocysteine and the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene are risk factors for stroke. The aim of the present study was to investigate the association between the 2 factors and stroke in Chinese in a large case-control study. Methods— We recruited 1823 stroke patients (807 cerebral thrombosis, 513 lacunar infarction, 503 intracerebral hemorrhage) and 1832 controls. Total plasma homocysteine was determined by high-performance liquid chromatography. C677T polymorphism was genotyped by polymerase chain reaction and Hin fI digestion. Results— Total plasma homocysteine levels were significantly higher in cases than controls (median, 14.7 versus 12.8 μmol/L; P P P P =0.017). The TT genotype was associated with an increased risk for overall stroke (odds ratio, 1.27; 95% CI, 1.04 to 1.56) and thrombotic stroke (odds ratio, 1.37; 95% CI, 1.06 to 1.78). Conclusions— The C677T polymorphism of the MTHFR gene was associated with increased risk of cerebral thrombotic stroke in Chinese. Total plasma homocysteine was correlated with both ischemic and hemorrhagic stroke, suggesting potential initiation of homocysteine-lowering therapy in this population.

Background and Purpose— It is still inconclusive whether high plasma lipoprotein(a) [Lp(a)] level is a risk factor for stroke. Small sample size and different ethnic groups and methodologies might be contributors to the conflicts in study results. The purpose of the present study was to investigate the association between plasma Lp(a) levels, pentanucleotide TTTTA repeat (PNTR) polymorphism of the apolipoprotein(a) [apo(a)] gene, and Chinese stroke in a case-control study. Methods— We recruited 1825 cases with stroke (44.3% cerebral atherothrombosis, 28.3% lacunar infarction, and 27.3% intracerebral hemorrhage) and 1817 controls from 7 centers in China. Lp(a) concentrations were quantified by enzyme-linked immunosorbent assay. The PNTR polymorphism of the apo(a) gene was determined by polymerase chain reaction–polyacrylamide gel electrophoresis. Conditional multivariate logistic regression analysis was used to identify independent risk factors for stroke and its subtypes. Results— Lp(a) levels were significantly higher in cases than in controls (median, 28.5 versus 23.1 mg/dL; P Conclusions— Our results indicate for the first time that low numbers of apo(a) PNTR and plasma Lp(a) levels are independently associated with both ischemic and hemorrhagic stroke in Chinese.

To explore the correlation between computed tomographic (CT) vascular convergence sign and enhancement value in patients with pulmonary nodules.A total of 708 consecutive patients with pulmonary nodule received dual-source CT scan from January 2010 to January 2012. They were divided into vascular convergence sign group (including 4 subgroups) and non-vascular convergence sign group. Then the correlation between CT vascular convergence sign and enhancement values was analyzed.The enhancement values in vascular convergence sign group were significantly higher than those in non-vascular convergence sign group ((27.6 ± 10.5) vs (3.2 ± 2.8) HU, P = 0.000). The CT enhancement values in lesions tended to increase with the number of connecting blood vessels. However, no significant differences existed among the subgroups (P0.05). The accuracy of vascular convergence sign for detection of pulmonary malignant nodules was 84.9%, 70.6% and 60.3% according to the standards of CT enhancement values ≥ 15, 20, 25 HU respectively. The sensibility, specificity and accuracy of determining pulmonary malignant nodules were 97.2%, 68.8% and 93.7% according to the standard of vascular convergence sign. The accuracy of determining pulmonary nodules' CT enhancement values ≥ 15 HU was 88.1% according to the standard of vascular convergence sign.Vascular convergence sign may be used to indicate the enhancement of pulmonary nodules when CT enhancement images are not available.

Metabolic syndrome has received great attention because it poses a potential cardiovascular hazard, which increases the risk of lower extremity atherosclerosis. However, the relationship between the components of metabolic syndrome and the onset of chronic venous disorder of the lower extremities remains unexplained.This study investigated the characteristics of cardiometabolic risk factors of early chronic venous disorder of the lower extremities in subjects with cardiometabolic risk. The characteristics of risk factors and diabetes-related complications in diabetic patients with early chronic venous disorder of the lower extremities were also investigated. In addition, the association between early chronic venous disorder and atherosclerosis of the lower extremities was analysed. The study examined 782 subjects with cardiometabolic risk factors, including obesity, hypertension, diabetes mellitus and dyslipidaemia. Lower extremity venous function was measured by digital photoplethysmography.Women had a higher prevalence of early chronic venous disorder than did men (p 0.01). Male subjects with early chronic venous disorder had a higher systolic blood pressure than those with normal venous function (p 0.01), and female subjects with early chronic venous disorder had a higher fasting plasma glucose level than did controls (p 0.05). The prevalence of diabetes mellitus is also significantly higher in female patients with early chronic venous disorder (p = 0.000). Diabetic patients with early chronic venous disorder not only had higher fasting plasma glucose and total cholesterol levels but also had more serious macrovascular complications than the control group. The independent risk factors of early chronic venous disorder in female subjects with cardiometabolic risks were age and fasting plasma glucose in men it was only age Women face a two times greater risk than men. The independent risk factors of early chronic venous disorder in diabetic patients were age, gender, HbA1c and triglyceride levels Women had an almost 12 times greater risk of early chronic venous disorder than men. Among the diabetic patients, the prevalence of early chronic venous disorder did not differ by ankle-brachial index.Female subjects with cardiometabolic risk factors or female diabetic patients face a greater risk of early chronic venous disorder than do male subjects. Diabetic patients with early chronic venous disorder had more serious macrovascular complications than did the controls, and the early venous function was found to be correlated with the blood glucose level and triglyceride status.

To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients.Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent.(1) The control rate of systolic BP was lower in patients with dysglycemia than in patients without dysglycemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism.Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.

To explore the characteristics and related risk factors of arterial elasticity in persons with prehypertension, high-normal blood lipid and(or) impaired glucose regulation(impaired fasting glucose and(or) impaired glucose tolerance).After receiving physical and biochemical examinations, a total of 1238 persons were enrolled. Among them, the etiologies were prehypertension (n = 65), high-normal blood lipid (n = 156), impaired glucose regulation (n = 159), prehypertension and high-normal blood lipid (n = 85), prehypertension and impaired glucose regulation (n = 77), high-normal blood lipid and impaired glucose regulation (n = 55) and prehypertension, high-normal blood lipid and impaired glucose regulation (n = 9). Also 332 healthy subjects, 113 hypertensive patients, 150 hyperlipidemics and 37 diabetics were enrolled as controls. Systemic vascular compliance (SVC), systemic vascular resistance (SVR), brachial artery distensibility (BAD) were measured with Dynapulse 200 M (Pulse Metric, Inc., USA).In persons with prehypertension, SVC was lower than healty group ((1.14 ± 0.20) ml vs (1.26 ± 0.23) ml, P0.01)and higher than hypertensive group ((1.11 ± 0.18) ml, P = 0.011), SVR higher than healty group (157 ± 29) kPa×s×L(-1) vs (148 ± 25) kPa×s×L(-1), P = 0.012) and lower than hypertensive group ((166 ± 36) kPa×s×L(-1), P0.01)and BAD lower than healty group(5.93% ± 1.14% vs 6.50% ± 1.30%, P0.01). Among different groups with prehypertension, high-normal blood lipid and(or) impaired glucose regulation, SVC, SVR and BAD had significant differences. As indicated by multiple linear regression analysis, blood pressure was an independent risk factor of arterial elasticity.Vascular function becomes damaged in prehypertensive stage. As an independent risk factor, blood pressure had more potent effect than lipid and blood glucose. Multiple cardiovascular risk factors with high-normal value may affect vascular function more strongly.

At present, there are still significant barriers that impede the clinical use of hESCs and iPS cells, including ethics, immunorejection, tumorigenesis from hESCs, and teratoma formation from iPS cells. It is therefore necessary to search for alternative sources of stem cells. WJ-MSCs originate from embryonic epiblasts and possess properties intermediate between hESCs and adult stem cells. However, the stemness properties of molecules in WJ-MSCs remain unclear compared to those of hESCs. In the present study, we isolated WJ-MSCs by a nonenzymatic method. Further, using microarray analysis by Affymetrix GeneChip and functional network analyses, we determined the degree of expression of stemness genes exhibited by the Human Stem Cell Pluripotency array. We also defined a wide range of stem cell gene expression in the WJ-MSCs in comparison with hESCs. At the same time, the definitive markers of early cardiac precursor cells and more committed progenitors were further characterized in WJ-MSCs. Our results demonstrated for the first time that WJ-MSCs had significant expression of undifferentiated human embryonic stem cell core markers, such as SOX2, NANOG, LIN28, SSEA1, SSEA3, SSEA4, KLF4, c-MYC, CRIPTO, and REX1, with a relatively lower level of expression than in hESCs. We also found WJ-MSCs have high expression of early cardiac transcription factors, such as Flk-1, Isl-1, and Nkx2.5. Functional analysis revealed signature genes of WJ-MSCs with specific roles involved in immune, cytoskeletal, and chemokine regulation, cell adhesion, and cell signaling. Our study indicated that there is a significant overlap between the stemness genes expressed by hESCs and WJ-MSCs. WJ-MSCs harbor a true stem cell population and are promising cells for stem cell-based therapies.

Objective: Tissue kallikrein (TK) cleaves kininogen to produce the potent bioactive compounds kinin and bradykinin, which lower blood pressure and protect the heart, kidneys, and blood vessels. Reduction in TK levels is associated with cardiovascular disease and diabetes in animal models. In this study, we investigated the association of TK levels with event-free survival over 5 years in Chinese first-ever stroke patients. Methods: We conducted a case–control study with 1,268 stroke patients (941 cerebral infarction, 327 cerebral hemorrhage) and 1,210 controls. Plasma TK levels were measured with an enzyme-linked immunosorbent assay. We used logistic regression and Cox proportional hazards models to assess the relationship between TK levels and risk of first-time or recurrent stroke. Results: Plasma TK levels were significantly lower in stroke patients (0.163 ± 0.064mg/l vs 0.252 ± 0.093mg/l, p < 0.001), especially those with ischemic stroke. After adjustment for traditional risk factors, plasma TK levels were negatively associated with the risk of first-ever stroke (odds ratio [OR], 0.344; 95% confidence interval [CI], 0.30–0.389; p < 0.001) and stroke recurrence and positively associated with event-free survival during 5 years of follow-up (relative risk, 0.82; 95% CI, 0.74–0.90; p < 0.001). Compared with the first quartile of plasma TK levels, the ORs for first-ever stroke patients were as follows: second quartile, 0.77 (95% CI, 0.56–1.07); third quartile, 0.23 (95% CI, 0.17–0.32); fourth quartile, 0.04 (95% CI, 0.03–0.06). Interpretation: Lower plasma TK levels are independently associated with first-ever stroke and are an independent predictor of recurrence after an initial stroke. ANN NEUROL 2011

To assess whether variants in the vascular endothelial growth actor receptor 2 (VEGFR-2) gene confer susceptibility to stroke risk.Association between gene variant rs2305948 (Val297Ile) and the risk of stroke was investigated in a multi-center case-control study, which comprised of 1849 patients with stroke (812 cerebral atherothrombosis, 530 lacunar infarction, and 507 intracerebral hemorrhage) and 1798 controls, and then replicated in the second independent stroke study (327 cases and 327 controls). The effect of Val297Ile on the binding ability of VEGFR-2 to VEGF was determined by a radioligand binding assay.The frequencies of carriers with variant 297Ile were significantly higher in patients with hemorrhagic stroke than in controls [297Val/Ile: 155(30.6%) versus 351 (19.5%), 297Ile/Ile: 18 (3.2%) versus 16 (1.0%); P0.01]. The variant 297Ile was significantly associated with increased risk of hemorrhagic stroke (odds ratio 2.25, 95% confidence interval 1.70-2.96; P0.01), and replication in the second stroke study obtained similar results. The substitution of Val to Ile at the amino acid residue 297 led to an increased equilibrium dissolved constant between VEGF and its receptor VEGFR-2 [297Val (87 +/- 9) pmol/L versus 297Ile (195 +/- 36) pmol/L, P0.01].The VEGFR-2 gene variants may serve as novel genetic markers for the risk of hemorrhagic stroke.

We previously reported that intracoronary implantation of bone marrow mononuclear cells (BMMC) into ischemic hearts improved cardiac function after myocardial infarction. However, the mechanisms have not been elucidated. The present study investigates whether apelin, a newly described inotropic peptide with important cardiovascular regulatory properties, contributes to the functional improvement in patients with severe heart failure after cell transplantation. Forty consecutive patients with severe heart failure secondary to myocardial infarction were assigned to the BMMC therapy group or the standard medication group according to each patient's decision on a signed consent document. In 20 patients intracoronary cell infusion was performed, and another 20 patients were matched to receive standard medication as therapeutic controls. An additional 20 healthy subjects were designated as normal controls. Clinical manifestations, echocardiograms, and biochemical assays were recorded. Plasma apelin and brain natriuretic protein (BNP) levels were determined by enzyme immunoassay. Baseline levels of plasma apelin were significantly lower in all heart failure patients compared to normal subjects. In patients who underwent cell transplantation, apelin increased significantly from 3 to 21 days after operation, followed by significant improvement in cardiac function. In parallel, BNP varied inversely with the increase of apelin. In patients receiving standard medical treatment, apelin remained at a lower level. Our findings indicated that increased apelin levels following cell therapy may act as a paracrine mediator produced from BMMCs and play an important role in the treatment of heart failure through autocrine and paracrine mechanisms.

Plasma homocysteine concentrations have been associated with the risk of stroke, but its relevance to secondary vascular events and mortality after stroke remains unclear because of inconsistent results from clinical trials. The aim of the present study was to investigate whether plasma homocysteine levels and the MTHFR (methylenetetrahydrofolate reductase) variant C677T contributed to the risk of stroke recurrence and all-cause mortality in a large prospective cohort of stroke patients in a Chinese population. A total of 1823 stroke patients (age, 35–74 years) were recruited during 2000–2001 and prospectively followed-up for a median of 4.5 years. During the follow-up, 347 recurrent strokes and 323 deaths from all-causes were documented. After adjustment for age, gender and other cardiovascular risk factors, a high homocysteine concentration was associated with an increased risk of 1.74-fold for stroke recurrence {RR (relative risk), 1.74 [95% CI (confidence interval), 1.3–2.3]; P

To compare the values of measurements of obesity, including body mass index(BMI), waist circumference (WC), waist-to-hip ratio (WHR), bioelectrical impedance analyzer(BIA) (fat mass and FAT%), ultrasonography (US) (subcutaneous fat distance and intraabdominal fat distance), and computed tomography (CT) in predicting the quantification of visceral adipose in abdominal obesity, and to evaluate the best cut-off point, sensitivity and specificity of these methods.4,301 inpatients with hypertension, 2,155 males and 2,146 females, aged (56.4 +/- 13.8) (11 - 89), all with at least 1 risk factor of cardiovascular diseases, underwent simple body fat measurement. 3458 received BIA, 2,553 received B mode ultrasonography, 1039 underwent CT examination, and 659 received all kinds of examination. Abdominal visceral adipose area (VA) measured with CTor= 100 cm(2) was the diagnostic criteria of visceral fat obesity (VFO). Receiver operating characteristic (ROC) curve was used to analyze the body fat indexes to determine the best cut-off point.(1) It was accurate for WC, fat mass, BMI, intraabdominal fat distance, FAT%, and WHR were all accurate in diagnosis of VFO with the values of area under ROC of 0.730 - 0.867. WC was the most effective measurement. (2) The best cut-off points of these methods in predicting abdominal visceral obesity in males and females were as follows: WC: 89.5 cm and 85.5 cm for WC. 25 kg/m(2) and 26 kg/m(2) for BMI, 0.97 and 0.95 for WHR, 29% and 38% for fat composition, 18.6 kg, and 20.4 kg for fat mass, and 38.5 mm and 34.7 mm for intraabdominal fat distance.WC, fat mass, BMI, intraabdominal fat distance, simple fat parameters, and WHR all can predict visceral adipose in abdominal obesity, in which WC is the best. For a given WC, the type of obesity can be determined by BIA and US.

To explore the relationship of different types of abdominal obesity to risk of metabolic syndrome (MS).Visceral fat area (VA) and substantial fat area (SA) were assessed by CT in 846 patients, 470 males and 376 females, aged 55 +/- 12, who suffered from at least one cardiometabolic risk factor and divided into 4 groups according to their VA and waist circumference (WC): non-obesity, masked visceral fat obesity (VFO), pseudo-VFO, and VFO groups. Blood pressure, fasting blood glucose, fasting serum insulin, and lipid profile were also measured. The MS risks of different types of abdominal obesity were compared.The prevalence rate of masked VFO of males was 10.9% (51/470), significantly higher than that of female (4.8%, 18/376). The prevalence rate of MS of the male patients with masked VFO was 43.1%, significantly higher than that of those in non-obesity group (25.0%), and lower than those of the males in the pseudo-VFO group (78.7%) and in the VFO group (88.6%), whereas the MS prevalence rate of the males in the pseudo-VFO group was significantly higher than those in the non-obesity and masked VFO groups. On the other hand, the MS prevalence rate of the female patients with masked VFO was 33.3%, not significantly different from that of the female patients in the non-obesity group (31.2%), but significantly lower than those of the pseudo-VFO and VFO groups (78.7% and 90.9% respectively). The MS prevalence rate of the female pseudo-VFO patients was also significantly higher than those in the non-obesity and masked VFO groups. Logistic regression analysis showed that WC and VA were independent risk factors for MS [OR (95% CI) = 1.13 (1.10-1.17), 1.01 (1.01-1.02), respectively, P0.01).Different types of abdominal obesity have important impacts on the risk of metabolic syndrome. Masked VFO, even though with normal WC, and pseudo-VFO have considerably higher cardiometabolic risks.

To contrastive analyze the population characteristics and individual variations of enhancement modes of normal pancreas and aorta at intravenous injection rates of 3 mL/s and 2 mL/s.Sixty-seven patients with normal pancreas were selected, and were divided randomly into 2 groups with different intravenous injection rates (3 mL/s for 35 patients in Group A and 2 mL/s for 32 patients in Group B). Single-level serial dynamic CT scan was performed at the level where the pancreas was best demonstrated. The enhancement values of pancreas and aorta for each time point of each patient were calculated, and the time-density curves of enhancement of pancreas and aorta of each patient were obtained. The peak enhancement and the time to reach the peak enhancement of pancreas and aorta of each individual patient were evaluated, and the 2 groups were compared. The individual variations of the enhancement modes of pancreas and aorta in each group were analyzed.The peak enhancement of pancreas was (75.7+/-17.0) Hu at (43.9+/-6.6) s for Group A, and (66.5+/-16.0) Hu at (55.2+/-5.0) s for Group B; the peak enhancement of aorta was (226.2+/-35.2) Hu at (35.4+/-4.5) s for Group A, (182.8+/-32.8) Hu at (48.0+/-3.7) s for Group B. There were significant differences in both the peak enhancement and the time to reach the peak enhancement of pancreas and aorta between the 2 groups. The coefficients of variation of time to reach the peak enhancement for pancreas and aorta were 15.0% and 12.7% in Group A, and 9.2% and 7.7% in Group B, respectively. The temporal windows of the optimal enhancement of pancreas were (9.7+/-4.5)s and (13.7+/-3.6)s in Group A and B, respectively.Better enhancement of pancreas and aorta is obtained at 3 mL/s than 2 mL/s, the time to reach the peak enhancement of pancreas and aorta is comparatively earlier at 3 mL/s than 2 mL/s, and the temporal windows of optimal enhancement of pancreas and aorta are comparatively shorter at 3 mL/s than 2 mL/s.

To investigate the long-term effect and safety of intracoronary autologous bone marrow mononuclear cell (BMMC) transplantation in patients with ischemic heart disease (IHD).Seventy-six patients with IHD, 26 patients with acute myocardial infarction (AMI) and 26 patients with chronic ischemic heart failure (CIHF), underwent routine treatment plus intracoronary autologous BMMC transplantation, and 24 patients, including 10 patients with AMI and 14 patients with CIHF underwent routine treatment as controls. Autologous BMMC transplantation was performed via a balloon catheter placed into the infarct-related artery during balloon dilatation by high pressure infusion to occlude the artery, which was performed 6 - 8 times for 2 minutes each with 2-minute interval or via a balloon catheter without occluding the infarct-related artery. Follow-up was conducted for 2 years.The surgery was safety without major periprocedural complications. There were no other new arrhythmias found by Holter recorder during the 2-years follow-up. In the AMI patients receiving BNNC transplantation, the left ventricular ejection fraction (LVEF) 1 and 2 years later increased by 5.79% (P0.05), 3.79% (P0.05) respectively; but there was no change in left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV). The LVEF 1 and 2 years later of the control group increased by 8.8% and 9.2% respectively (both P0.01) and the LVESV 1 and 2 years later decreased by 20.4% and 27.8% respectively (both P0.05), the myocardium defect area 2 years later was not significantly different from that 3 months later. The heart function of the control group became markedly worse.Autologous BMMC intracoronary transplantation is safe and effective, especially in patients with CIHF.

To observe the relationship between abdominal obesity and left ventricular weight/function.A total of 495 patients [265 males, mean age (55 +/- 12) years] with hypertension (139), diabetes (65), metabolic syndrome (285), diabetes complicated with hypertension (11) were enrolled in this study. Visceral adipose area (VA), the subcutaneous adipose (SA), the total abdominal adipose (TA) were measured by computerized tomography (CT) and left ventricular weight and function were obtained by echocardiography. Patients were divided into three groups according to the VA (I. VA75 cm(2), n=173, II. VA75 and110 cm(2), n=153, III. VAor= 110 cm(2), n=169).Left ventricular mass (LVM) and LVM index (LVMI) increased and LVEF and E/A decreased in proportion to increasing VA. Left ventricular hypertrophy (LVH) rate was significantly higher in group II and III compared to group I and LVEF was significantly reduced in group III compared to group I and II. There are significant correlation between LVMI and VA, SA, TA as well as between LVEF and VA after adjusting gender, age and blood pressure. Logistic regression analysis showed that VA is an independent predictor for LVH.The abdominal adipose accumulation is closely related to the left ventricular weight and function.

Activation of nonselective cation channels of the transient receptor potential canonical (TRPC) family has been associated with hypertension. Whether store-operated channels, which are activated after depletion of intracellular stores, or second-messenger-operated channels, which are activated by 1-oleoyl-2-acetyl-sn-glycerol, are affected in essential hypertension is presently unknown.Using a polymerase chain reaction, an in-cell western assay and the fluorescent dye technique we studied TRPC3, TRPC5, and TRPC6 expression and store-operated and 1-oleoyl-2-acetyl-sn-glycerol-induced calcium influx into human monocytes in 19 patients with essential hypertension and in 17 age-matched and sex-matched normotensive control individuals.We observed a significantly increased expression of TRPC3 and TRPC5, but not TRPC6, in essential hypertension. Store-operated calcium influx was significantly elevated in essential hypertension. Store-operated calcium influx was reduced by the inhibitor 2-aminoethoxydiphenylborane, specific TRPC3 and TRPC5 knockdown, but not TRPC6 knockdown using gene silencing by RNA interference. 1-Oleoyl-2-acetyl-sn-glycerol-induced calcium influx and barium influx were also significantly elevated in essential hypertension. The 1-oleoyl-2-acetyl-sn-glycerol-induced cation influx was reduced by TRPC3 and TRPC5 knockdown.We demonstrated an increased TRPC3 and TRPC5 expression and a subsequently increased store-operated calcium influx and increased 1-oleoyl-2-acetyl-sn-glycerol-induced cation influx in monocytes of patients with essential hypertension. This increased activation of monocytes through TRPC channels in patients with essential hypertension may promote vascular disease in these patients.

We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect of TRPV1 on cytosolic calcium was determined fluorometrically in 3T3-L1-preadipocytes and in human visceral fat tissue. Adipogenesis in stimulated 3T3-L1-preadipocytes was determined by oil red O-staining of intracellular lipid droplets, triglyceride levels, expression of peroxisome proliferator-activated receptor-γ, and expression of fatty acid synthase. Long-term feeding experiments were undertaken in wild-type mice and TRPV1 knockout mice. We detected TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans. In vitro, the TRPV1 agonist capsaicin dose-dependently induced calcium influx and prevented the adipogenesis in stimulated 3T3-L1-preadipocytes. RNA interference knockdown of TRPV1 in 3T3-L1-preadipocytes attenuated capsaicin-induced calcium influx, and adipogenesis in stimulated 3T3-L1-preadipocytes was no longer prevented. During regular adipogenesis TRPV1 channels were downregulated which was accompanied by a significant and time-dependent reduction of calcium influx. Compared with lean counterparts in visceral adipose tissue from obese db/db and ob/ob mice, and from obese human male subjects we observed a reduced TRVP1 expression. The reduced TRPV1 expression in visceral adipose tissue from obese humans was accompanied by reduced capsaicin-induced calcium influx. The oral administration of capsaicin for 120 days prevented obesity in male wild type mice but not in TRPV1 knockout mice assigned to high fat diet. We conclude that the activation of TRPV1 channels by capsaicin prevented adipogenesis and obesity.

To investigate the chronic effects of intracoronary autologous bone marrow mononuclear cell (BM-MNCs) transplantation in patients with refractory heart failure (RIHF) after myocardial infarction.Thirty patients with RIHF (LVEF40%) were enrolled in this nonrandomized study, autologous BM-MNCs (5.0 +/- 0.7) x 10(7) were transplanted with via infarct-related coronary artery in 16 patients and 14 patients received standard medical therapy served as control. Baseline and follow up evaluations included complete clinical evaluations, plasma BNP, ANP, ET-1 measurements, echocardiography, PET, and Holter monitoring.Baseline characteristics were similar between the 2 groups. There were no major periprocedural complications. One patient developed ventricular premature contractions during cell infusion for several seconds and recovered spontaneously. Compared to pre-transplantation, plasma BNP and ET-1 significantly decreased and plasma ANP significantly increased at 7 days post transplantation; 6 minutes walking distance increased from (72.1 +/- 31.5) to (201.6 +/- 23.3) m (P0.01), LVEF increased 9.9% (P0.001) and FDG-PET revealed vital myocardium area increased (10.3 +/- 3.4)% (P0.01) at 3 months after BM-MNCs transplantation. At 6 months follow up, the NYHA class improved from (3.4 +/- 0.1 to 2.4 +/- 0.2, P0.001) and no patient died and 1 patient rehospitalized due to lower extremities edema. In control group, LVEF decreased 7.2% compared to baseline (P0.001) and was significantly lower than transplantation group at 3 months (P0.001). At 6 months follow up, the NYHA class increased from (3.5 +/- 0.1 to 3.9 +/- 0.1, P0.05), 2 patients died and 10 patients rehospitalized due to aggravated heart failure.Present study demonstrates that intracoronary transplantation of autologous BM-MNCs is safe and effective for treating patients with RIHF after myocardial infarction.

To investigate the relationship between PPARdelta + 294T/C gene polymorphism and lipid profile, obesity and left ventricular hypertrophy (LVH) in patients with metabolic syndrome (MS).This study was conducted in 300 patients with MS and 174 patients with essential hypertension (EH) and 143 patients with type 2 diabetes mellitus (T2DM). MS was diagnosed according to 1999 WHO criteria. Fasting insulin (FINS), fasting blood glucose (FBG), plasma lipids levels were measured, LVH was examined by Doppler echocardiography. The PPARdelta + 294T/C gene polymorphism were analyzed using polymerase chain reaction and subsequently digested by BSLI restriction endonuclease.The frequencies of the PPARdelta + 294T/C genotypes were not different among three groups. Compared with T2DM and EH, MS patients had significantly higher body mass index (BMI), plasma total cholesterol, TG and LDL-C levels (P0.01 or P0.05). LVM, LVMI and incidence rate of LVH were significantly higher in MS and EH patients than that in T2DM (P0.01). MS patients with CC genotype had significantly higher total cholesterol and LDL-C levels than those with TT and TC genotypes (total cholesterol in CC genotype: 6.13 +/- 1.86 mmol/L vs in TC genotype: 5.14 +/- 1.10 mmol/L, P0.05, and CC genotype: 6.13 +/- 1.86 mmol/L vs TT genotype: 4.99 +/- 1.42 mmol/L, P0.01; LDL-C in CC genotype: 3.82 +/- 1.52 mmol/L vs in TC genotype: 3.14 +/- 0.88 mmol/L, P0.05, and in CC genotype: 3.82 +/- 1.52 mmol/L vs in TT genotype: 2.90 +/- 0.87 mmol/L, P0.01). BMI and LVMI in MS patients with C allele carriers (CC + TC) were significantly higher than that of TT genotype (LVMI in CC + TC: 46 +/- 10 g/m(2.7) vs in TT: 44 +/- 10 g/m(2.7); BMI in CC + TC: 26 +/- 3 kg/m(2) vs in TT: 25 +/- 3 kg/m(2), P0.05).It is indicated that PPARdelta + 294T/C gene polymorphism in subjects with MS may be involved in the occurrence of obesity and dyslipidemia. MS patients with C allele had a predominant LVH than subjects with TT genotype.

To investigate the regulation of calcium sensitive signal substance calpain in signal transduction of myocardial remodeling in patients with congestive heart failure.All 39 congestive heart failure (CHF) patients with rheumatic mitral valve stenosis disease were selected and 38 cases of healthy persons were included as controls. Cardiac function parameters were measured by echocardiography. The concentration of angiotension II (AngII) in plasma and myocardial tissues was determined by radio immunoassay (RIA). Western blot was used to assay the protein expression of calpain, cain/cabin 1, cain/cabin 1Delta, and calcineurin (CaN) phosphorylation.The AngII concentrations in the plasma and myocardial tissues in patients with CHF were higher than those in the control group. Meanwhile the AngII concentrations positively correlated to the parameters of the cardiac dilation respectively but negatively correlated to the parameters of cardiac function. Pathological changes of myocardial tissues in CHF with valvular heart disease showed typical myocardial remodeling. The hypertrophy was dominant at early stage of CHF, while at the end stage the characteristics include disordered alignment of the myocytes, the discontinuity and dissolving of cardiomyofibrills, destroyed subcellular organs, and the hyperplasia of interstitial tissue. Compared to the control group, u-calpain, m-calpain, and cain/cabin 1Delta protein expression, CaN phosphorylation in myocardial tissues in CHF groups were highly expressed and their expressions were positively correlated to the severity of CHF. The expression of cain/cabin1 deceased and its expression was negatively correlated to the severity of CHF.The degradation of cain/cabin 1 by calpain may play an important role by causing the activation of CaN signal pathway in myocardial remodeling mediated by renin angiotension system in CHF.

To explore the obesity distribution in old people and the relation between senile obesity and health.First, a questionnaire was designed which included chronic disease history, body mass index (BMI), physiological value, biochemistry index, anti-oxidation index, diagnosis of diseases, etc. Second, the measure and detection methods were unified; and the last, the investigation was made along with daily clinical work by clinicians.We received 391 questionnaires. The overweight rate was 36.1% and the obesity rate was 7.9% . Total anti-oxidation activity in serum (TAS) and superoxide dismutase (SOD) decreased with body mass index (BMI), and the value in the obesity group was the lowest; Malonaldehyde (MDA) of overweight obesity was the largest. The mean blood pressure, blood fat, and blood glucose as well as the prevalence of cardiovascular disease, hyperlipemia, and glycuresis increased with BMI; and the value in the obesity group was the largest.The prevalence of the senile obesity was below the average and the senile obesity complications were various and serious, and perhaps related to imbalance of free radical's production and cleanup, so the senile obesity seriously harmed old people's health.

To assess the relationship between PPAR gamma C161-T polymorphism and Carotid Atherosclerosis in metabolic Syndrome (MS).Polymerase chain reaction-restricted fragments length polymorphism was used to study the distribution of the PPAR gamma C161-T polymorphism in 248 metabolism syndrome, 163 essential hypertension (EH) and 115 type 2 diabetes mellitus (DM) patients and 121 normal controls. Fasting insulin (FINS), fasting blood glucose (FBG), uric Acid (UA), plasma lipids and ultrasonography for carotid artery were examined.Waistline and BMI were significantly higher in MS compared with those in control, EH and DM (P0.01). systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were markedly higher in MS and EH compared with those in DM and control (P0.01). The frequencies of the CC, CT and TT were 74.6%, 21.8% and 3.6% in MS respectively, The frequencies of the CC was significantly higher in MS compared with that in control, but T allele carrier (CT + TT) was significantly lower compared with control, DM and EH (P0.05 or P0.01). In MS, CC genotype had significantly increased the intima-media thickness (IMT) of common carotid artery and plaque index compared with CT + TT (IMT: 0.84 mm +/- 0.3 mm vs 0.66 mm +/- 0.19 mm; plaque index: 2.19 +/- 1.21 vs 1.66 +/- 1.36, P0.05), CC genotype had significantly increased plaque index compared with CT + TT in EH and DM (plaque index: EH: 1.55 +/- 1.23 vs 1.29 +/- 0.92; DM: 1.57 +/- 1.2 vs 1.18 +/- 0.85, P0.05); CC genotype had significantly higher SBP compared with CT + TT in EH (P0.05), CC genotype had significantly increased plaque index in MS than that in DM and EH (P0.01), CC genotype had significantly increased IMT in MS compared with DM. CC genotype had significantly higher SBP and PP compared with CT + TT in MS (SBP: 155 mm Hg +/- 23 mm Hg vs 145 mm Hg +/- 21 mm Hg; PP: 69 mm Hg +/- 8 mm Hg vs 58 mm Hg +/- 8 mm Hg, 1 mm Hg = 0.133 kPa, P0.05).In MS, CC genotype was prone to lesion of carotid artery, but CT + TT may reduce lesion of carotid artery, which implicates that PPAR gamma C161-T may play a important role in carotid artery arteriosclerosis.

To assess the association of the metabolic syndrome with stroke in Chinese using the definition of ATP III, and revised definition according to Chinese criteria for abdominal obesity.Multi-center case control study, 1934 first-ever-stroke patients (Atherothrombosis, lacunar infarction, and intracerebral hemorrhage) aged 30 to 74 years were sequentially recruited. And 1839 age, gender and geographically matched subjects were included as controls.The prevalence of metabolic syndrome defined by either ATP III or Chinese criteria was significantly increasing in patients with lacunar infarction, cerebral atherosclerosis, or intracerebral hemorrhage than control subjects. After age- and sex-adjusted and further adjusted age, sex, total cholesterol, smoking, drinking, and education levels, the metabolic syndrome defined by ATP III criteria was associated with a 2.7 to 4.3 fold and 2.5 to 4.0 fold higher risk of the three stroke subtypes, respectively.the metabolic syndrome defined by ATP III and revised according to Chinese criteria of abdominal obesity was positively associated with the risk of stroke in our case control study. This study underscores the need for well-designed prospective study in Chinese to give further evidence to the link between metabolic syndrome and stroke.

To explore the relationship between genetic anomaly and risk factors in hypertension, a polymorphism at position G894T of the gene encoding the endothelial nitric oxide synthase (eNOS) together with hypertension related risk factors were observed in patients with essential hypertension (EH) in Chongqing city.Two hundred and twenty-six patients with EH and matched controls were selected. Genotypes of polymorphisms were determined by polymerase chain reaction (PCR), while PCR products were digested by restriction endonuclease (BanII). Questionnaire referred to life style, dietary, smoking, alcohol consumption, psychological and mental state, waist-to-hip ratio (WHR), etc was administered.There was no significant difference noticed in genotype distribution for the eNOS gene G894T genotype between hypertensive groups and controls, but difference was found among certain related risk factors, such as salt intake, snoring and WHR, etc. Logistic regression analysis showed no association between 894T allele and hypertension.Although the polymorphism of eNOS gene G894T did not seem to play an important and direct role in the pathogenesis of EH it might have indirect effects through certain risk factors.

To explore the association between alpha-adducin (ADD1) G/W460 and intracerebral hemorrhage (ICH) in Chinese.Samples of peripheral blood were collected from 456 patients with ICH diagnosed by CT or MRI from 7 clinical centers in China and 454 age, sex, and geographically matched subjects as controls. The ADD1 G/W460 polymorphism was detected by PCR. Information about prior exposure to various potential risk factors was collected by questionnaire survey.The distribution of ADD1gene G460W polymorphisms in the ICH patients and controls were in agreement with the Hardy-Weinberg proportion. The prevalence of 460W allele among ICH cases was 82.2%, higher than that in the controls (76.0%, crude odds ratio, 1.46; 95% CI, 1.05 to 2.05). The ADD1 460W allele was still significantly associated with ICH after adjustment for hypertension and other ICH putative risk factors (adjusted odds ratio, 1.38; 95% CI, 1.01 to 1.88).Alpha-adducin gene G/W 460 polymorphism is significantly associated with the risk of ICH. This association does not appear to be mediated by established ICH risk factors, specifically hypertension status.

To investigate the relationship between small, dense LDL (sLDL) and stroke in Chinese population.The plasma level of sLDL was examined by 2% - 16% nondenatured gradient gel electrophoresis in 204 patients with stroke, including 103 cases of ischemic cerebral infarction (ICI), 51 cases of lacunar infarction (LI), and 50 cases of subcortical hemorrhage (SH), and in 341 sex- and age-matched controls in China. Traditional risk factors for stroke were investigated as well.The plasma level of sLDL was significantly higher in patients with ICI and LI (54 +/- 8% and 52 +/- 7%) than in the controls (47 +/- 11%, both P0.01). However, the plasma sLDL of the CH patients was 50 +/- 9%, not significantly different from that of the controls (P0.05). Multiple stepwise regression analysis showed that sLDL was significantly associated with systolic blood pressure, age, and the levels of triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (all P0.05). Multivariate logistic regression analysis showed that those with sLDL50% had increase of risk of ischemic cerebral infarction (OR = 3.1, 95% CI 1.649 - 5.691, P0.001) independent of other risk factors. The relationship between sLDL abnormality and LI and between sLDL abnormality and SH had no statistical significance (both P0.05).sLDL is significantly associated with ischemic cerebral infarction independent of other risk factors in Chinese population. sLDL may be a new marker for stroke at least in this Chinese population.

To study the structure and function of the carotid artery in the metabolic syndrome (MS).171 patients were divided into three groups: metabolic syndrome (MS), diabetes mellitus (DM), and essential hypertension (EH). Plasma lipids and ultrasonography for carotid artery were examined.Levels of TG, LDL, ApoB were significantly higher in MS as compared with those EH (P0.01, 0.05, 0.01). Levels of TG were higher in MS as compared with those in DM (P0.01). The carotid resistance index and the intima-media thickness (IMT) of common carotid artery were significantly higher in MS as compared with those in DM or EH (P0.05). The occurrence rate of carotid plaque and plaque index was higher in patients with MS than that in patients with EH or DM (P0.01, 0.01).Clustering of multiple cardiovascular risk factors can cause more severe atherosclerosis of carotid artery in MS.