Rac1b enhances cell survival through activation of the JNK2/c-JUN/Cyclin-D1 and AKT2/MCL1 pathways.

Rac1b is a constitutively activated, alternatively spliced form of the small GTPase Rac1. Previous studies showed that Rac1b promotes cell proliferation and inhibits apoptosis. In the present study, we used microarray analysis to detect genes differentially expressed in HEK293T cells and SW480 human colon cancer cells stably overexpressing Rac1b. We found that the pro-proliferation genes JNK2, c-JUN and cyclin-D1 as well as anti-apoptotic AKT2 and MCL1 were all upregulated in both lines. Rac1b promoted cell proliferation and inhibited apoptosis by activating the JNK2/c-JUN/cyclin-D1 and AKT2/MCL1 pathways, respectively. Very low Rac1b levels were detected in the colonic epithelium of wild-type Sprague-Dawley rats. Knockout of the rat Rac1 gene exon-3b or knockdown of endogenous Rac1b in HT29 human colon cancer cells downregulated only the AKT2/MCL1 pathway. Our study revealed that very low levels of endogenous Rac1b inhibit apoptosis, while Rac1b upregulation both promotes cell proliferation and inhibits apoptosis. It is likely the AKT2/MCL1 pathway is more sensitive to Rac1b regulation.

A comparison of 2 devices for radial artery hemostasis after transradial coronary intervention.

BACKGROUND AND OBJECTIVE: Transradial access is an attractive approach for angiography or percutaneous coronary intervention. Different devices have been used to apply pressure locally at the site of arterial entry for achieving hemostasis. The aim of this study was to evaluate the effect of 2 different hemostatic devices on radial artery outcomes after transradial coronary intervention. SUBJECTS AND METHODS: This study included 600 patients who had undergone transradial coronary intervention who were randomized into 2 groups after the procedure: 300 were treated with a radial compression device (TR Band, Terumo Medical, Tokyo, Japan) (CD group) and the other 300 patients were treated using a chitosan-based pad (Anscare, Daxon, Taoyuan, Taiwan) (CS group). Compression time, major and minor access site bleeding complications, and incidence of radial artery occlusion were recorded. RESULTS: There were no statistical differences in the baseline clinical characteristics of the patients between the 2 groups. Compression time in the CS group was significantly shorter than that in the CD group (P < .001). Although no major access site bleeding complications were observed in either group, 6 patients in each group experienced minor access site bleeding complications. At the same time, 61 patients in the CD group and 21 patients in the CS group experienced errhysis (20% vs 7%, respectively; P < .001). Early radial artery occlusion (24 hours) occurred in 11.7% of the patients in the CD group and 5.4% of the patients in the CS group (P < .05). Chronic radial artery occlusion (30 days) occurred in 10% of the patients in the CD group and 5% of the patients in the CS group (P < .05). CONCLUSION: The application of the chitosan-based pad showed better hemostatic efficacy and a lower incidence of radial artery occlusion after transradial coronary intervention compared with the compression device.

Renoprotective effect of alprostadil in combination with statins in patients with mild to moderate renal failure undergoing coronary angiography.

BACKGROUND: The role of alprostadil and statins in contrast-induced acute kidney injury (CI-AKI) is controversial. The purpose of this study was to explore the efficacy of combined therapy with alprostadil and statins in protecting renal function and preventing contrast-induced nephropathy (CIN) in patients undergoing coronary angiography. METHODS: A total of 156 consecutive patients with mild to moderate renal failure who underwent coronary angiography were enrolled in our study, and randomly categorized into two groups. In the statins group, 80 patients were treated with statins before and after coronary angiography. In the alprostadil plus statins group, 76 patients were treated with statins and alprostadil before and after coronary angiography. Serum creatinine (SCr), serum cystatin (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) were detected after administration of contrast media, and adverse events were evaluated within six months. RESULTS: In both groups, the SCr, CysC and NGAL significantly increased after coronary angiography and peaked at 48, 24 and 6 hours, respectively. SCr, CysC and NGAL were significantly lower in the alprostadil plus statins group than in the statins group (P < 0.05). The incidence of CIN in the alprostadil plus statins group was slightly lower than in the statins group. The incidence of adverse events within six months in the alprostadil plus statins group was significantly lower than in the statins group (P = 0.034). CONCLUSIONS: Intravenous alprostadil in combination with oral statins is superior to statins alone for protecting renal function in patients with mild to moderate renal dysfunction who undergo coronary angiography, and can reduce the incidence of adverse events seen within six months.

[Peroxisome proliferator-activated receptor α/γ agonist tesaglitazar stabilizes atherosclerotic plaque in diabetic low density lipoprotein receptor knockout mice].

OBJECTIVE: To investigate the effects of peroxisome proliferator-activated receptor (PPAR) α/γ agonist on atherosclerotic plaque stabilization in diabetic LDL receptor knockout (LDLr-/-) mice. METHODS: Female 4-week-old LDLr-/- mice fed with high-glucose and high-fat diet for 4 weeks were randomly divided into three groups (n = 15 each): control group (only fed with high-glucose and high-fat diet), diabetic group [induced by high-glucose and high-fat diet combined with a low-dose of streptozotocin (STZ)] without tesaglitazar and with tesaglitazar (20 µg/kg oral treatment). After 6 weeks, the mice were sacrificed, body weight, fasting blood glucose (Glu), total cholesterol (TC), triglyceride (TG) levels were measured. The expression of ICAM-1, VCAM-1, MCP-1 in the brachiocephalic atherosclerotic lesions were determined by Western blot and immunohistochemistry, respectively. Brachiocephalic artery was prepared for morphologic study (HE, oil red O, Sirius red staining) and immunohistochemical analysis (macrophage surface molecule-3, α-smooth muscle actin), respectively. RESULTS: Serum TC [(32.34 ± 3.26) mmol/L vs. (16.17 ± 1.91) mmol/L], TG [(3.57 ± 0.99) mmol/L vs. (2.21 ± 0.11) mmol/L] and Glu [(15.21 ± 4.67) mmol/L vs. (6.89 ± 0.83) mmol/L] levels were significantly higher in diabetic group than in the control group (all P < 0.01). The expression of ICAM-1 (2.31 ± 0.35 vs.1.34 ± 0.21), VCAM-1 (1.65 ± 0.14 vs.0.82 ± 0.26), MCP-1 (2.27 ± 0.16 vs.1.56 ± 0.23) were significantly upregulated in diabetic group compared with control group (all P < 0.01). Brachiocephalic atherosclerotic plaque area [(4.597 ± 1.260)×10(3) µm(2) vs. (0.075 ± 0.030)×10(3) µm(2)], lipid deposition [(47.23 ± 2.64)% vs. (9.67 ± 1.75)%], Mac-3 positive area [(19.15 ± 3.51)% vs. (1.72 ± 0.16)%], α-smooth muscle actin [(5.54 ± 1.17)% vs. (2.13 ± 0.41)%] and collagen content [(4.27 ± 0.74)% vs. (0.43 ± 0.09)%] were all significantly larger/higher in diabetic LDLr-/- mice than in the control group (all P < 0.01). While tesaglitazar treatment significantly reduced serum TC [(30.47 ± 3.18) mmol/L], TG [(3.14 ± 0.71) mmol/L] and Glu [(7.92 ± 1.28) mmol/L] levels (all P < 0.01). Similarly, the expression of ICAM-1 [(1.84 ± 0.22)], VCAM-1 [(1.27 ± 0.11)], MCP-1 [(1.83 ± 0.24)], brachiocephalic atherosclerotic lesion area[(1.283 ± 0.410)×10(3) µm(2)], lipid deposition[(23.52 ± 1.39)%] were also significantly reduced by tesaglitazar (all P < 0.05). Moreover, tesaglitazar increased α-smooth muscle actin [(9.46 ± 1.47)%] and collagen content [(6.32 ± 1.15)%] in diabetic LDLr-/- mice (all P < 0.05). In addition, lipid deposition and Mac-3 positive areas [(10.67 ± 0.88)% vs. (15.83 ± 1.01)%] in the aortic root were also reduced in tesaglitazar treated diabetic LDLr-/- mice (P < 0.01). CONCLUSIONS: Tesaglitazar has anti-inflammatory effects in the diabetic LDLr-/- mice. Tesaglitazar could reduce lipid deposition, increase collagen and α-SMA content in the brachiocephalic atherosclerotic lesions, thus, stabilize atherosclerotic plaque in this model.

Vaspin plasma concentrations and mRNA expressions in patients with stable and unstable angina pectoris.

BACKGROUND: Vaspin was a recently identified adipokine, playing a protective role in many metabolic diseases. The present study aimed to investigate the association between vaspin plasma level and stable angina pectoris (SAP) and unstable angina pectoris (UAP). METHODS: A total of 88 patients with angiographically-proved coronary artery disease (CAD) (SAP 47, UAP 41) and 103 control subjects without cardiovascular diseases were enrolled in this study. Circulating vaspin, mRNA expression of vaspin in peripheral blood mononuclear cells (PBMC), clinical parameters, lipid profile and high-sensitivity C-reactive protein (hsCRP) were assayed. The severity of CAD was also assessed according to the number of vessels diseased. RESULTS: There are significant differences in circulating vaspin levels and mRNA levels of PBMC between SAP and UAP groups (SAP 0.91±0.95 ng/mL and UAP 0.43±0.38 ng/mL, p<0.01 in circulating vaspin level; SAP 1.19±0.85 and UAP 0.82±0.56, p<0.05 in mRNA level of PBMC). An inverse correlation between the number of diseased vessels and plasma vaspin concentration was observed (r=-0.350, p<0.01) in the CAD group. Construction of receiver operating characteristic curves confirmed that vaspin plasma concentrations significantly differentiated CAD patients (area under the curve=0.684, p<0.001), as well as UAP (area under the curve=0.640, p<0.05). CONCLUSION: Decreased vaspin plasma levels and mRNA levels in PBMC were observed in patients with UAP. Low vaspin concentrations correlate with CAD severity. The findings suggested that vaspin could serve as a novel biomarker of CAD as well as UAP.

Increased serum myeloid-related protein 8/14 level is associated with atherosclerosis in type 2 diabetic patients.

BACKGROUND: Myeloid-related protein 8/14 (MRP8/14) is a stable heterodimer formed by two different calcium-binding proteins (MRP8 and MRP14). Studies have identified that MRP8/14 regulates vascular inflammation and serves as a novel marker of acute coronary syndrome. In this study, we evaluated the correlation between serum levels of MRP8/14, hsCRP, endogenous secretory receptor for advanced glycation end-products (esRAGE) and the occurrence of coronary artery disease (CAD), or carotid intima-media thickness (IMT) when CAD was not yet developed in diabetic patients. METHODS: Serum levels of MRP8/14, esRAGE and hsCRP were measured in 375 diabetic patients. Then the results of those who had CAD were compared against who had not. Also, we investigated the associations between above-mentioned indicators and IMT of subjects without CAD in both diabetic group and non-diabetic one. RESULTS: Serum MRP8/14 was significantly higher in CAD than in non-CAD group (9.7 ± 3.6 ug/ml vs. 8.2 ± 3.0 ug/ml, P < 0.001). It was associated with severity of CAD (r = 0.16, P = 0.026). In non-CAD group, MRP8/14 was associated with IMT in patients with (r = 0.30, P < 0.001) or without diabetes (r = 0.26, P = 0.015). The areas under the curves of receiver operating characteristic for CAD were 0.63 (95% CI 0.57-0.68) for MRP8/14, 0.76 (95% CI 0.71-0.81) for hsCRP and 0.62 (95% CI 0.56 -0.67) for esRAGE. CONCLUSION: In summary, we report that diabetic patients with CAD had elevated plasma MRP8/14 levels which were also positively correlated with the severity of CAD and carotid IMT in patients without clinically overt CAD.

Comparative study of 4Fr catheters using the ACIST variable rate injector system versus 6Fr catheters using hand manifold in diagnostic coronary angiography via transradial approach.

BACKGROUND: The transradial approach is regarded as a useful vascular site for coronary procedures. The aim of this study was to test whether 4Fr catheters assisted by ACIST variable rate injector system can produce comparable angiographic quality and reduce the risk of radial artery injury compared to hand manifold 6 Fr catheters. METHODS: A total of 1816 patients were studied consecutively, among whom 856 patients received coronary angiography by 4 Fr catheters (4Fr group) and 960 patients by 6 Fr catheters (6Fr group). Angiographic and procedural characteristics were observed and recorded. The luminal inner radial arterial diameter before and after the procedure were collected. RESULTS: The baseline clinical characteristics were similar in both groups. There were no significant differences in procedure time, radiation dose and quality scores in both groups (P > 0.05), but more contrast media was delivered in the 6Fr group (P < 0.001). The mean radial arterial diameter six months after the procedure in the 6Fr group reduced significantly compared to that measured one day prior to the procedure (P < 0.001). CONCLUSIONS: Coronary angiography using the 4Fr catheters with Acist power injection system can achieve an acceptable diagnostic quality while at the same time minimizing radial artery injury and contrast media consumption.

Comparative study on transradial versus transfemoral approach for primary percutaneous coronary intervention in Chinese patients with acute myocardial infarction.

OBJECTIVE: To compare the transradial approach and transfemoral approach for primary percutaneous coronary intervention (PCI) in Chinese patients with acute myocardium infarction (AMI). METHODS: From August 2005 to September 2008, we randomly divided 200 AMI patients into transradial intervention (TRI) group and transfemoral intervention (TFI) group. The study took place in the Department of Cardiology, The Tenth People's Hospital, Tongji University, Shanghai, China. During the procedure, the puncture success, procedure success, infarction related artery (IRA), coronary flow, percentage of 3 vessel disease, stent used, and tirofiban used were observed. The procedural time intervals were also recorded. After the procedure, the major adverse cardiac events (MACEs) and the vascular complications were studied. In this trial, the hospital stay was also recorded. RESULTS: The baseline clinical characteristics of the patients were similar in both groups. There were no statistical differences in IRA, 3 vessel disease, initial and final thrombolysis in myocardial infarction (TIMI) flow, rate of stent and tirofiban used, and procedure rate (p>0.05). No statistical differences were observed in the puncture time, cannulation time, reperfusion time, procedural time, and fluoroscopy time in both groups (p>0.05). There was no statistical difference in the incidence of MACEs between the 2 groups (p>0.05). Not only the vascular complications were lower in the TRI group (p<0.01), but also the total hospital stay was longer in the TFI group than in the TRI group (p<0.001). CONCLUSION: Transradial intervention for Chinese patients with AMI yields comparable procedural success, and has fewer vascular access site complications compared with the TFI group.

A randomized prospective comparison of CartoMerge and CartoXP to guide circumferential pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation.

BACKGROUND: CartoXP and CartoMerge have been used to treat atrial fibrillation (AF) for several years. Our randomized prospective study compared clinical outcomes of these two versions of three dimensional electroanatomic mapping system in guiding catheter ablation for paroxysmal atrial fibrillation (PAF). METHODS: Eighty-one patients with symptomatic, drug refractory PAF were randomly assigned to CartoMerge group (n=42, mean age (54.5+/-13.1) years, history of AF=3.2 years) or CartoXP group (n=39, mean age (59.8+/-15.6) years, history of AF = 2.9 years). All patients underwent 64-slice computed tomography (MSCT) 1 to 3 days prior to ablation procedure. Using CartoMerge(TM) Image Integration Module, 3D anatomical images of the left atrium (LA) and pulmonary veins (PVs) derived from MSCT of CartoMerge group were established and merged with the electroanatomical map. The integrated images were used to guide the procedure of circumferential pulmonary vein isolation (CPVI). In the other group, CPVI was guided just by CartoXP. The endpoint of CPVI in both groups was abolition or dissociation of pulmonary vein potentials (PVPs). RESULTS: Mapping points to establish the electroanatomical model of the LA/PVs were 48.7+/-13.4 in CartoMerge group and 62.5+/-15.7 in CartoXP group (P<0.001). Mean distance between mapping points and the MSCT surfaces in CartoMerge group was (1.59+/-0.33) mm. Accomplishment of abolition or dissociation of PVPs was achieved 95.2% in CartoMerge group and 92.3% in CartoXP group. Durations of procedure and exposure to X-ray were (156+/-25) minutes, (179+/-21) minutes (P<0.001) and (19.6+/-7.5) minutes, (28.5+/-12.8) minutes (P<0.001), respectively. After a follow-up with duration of (11.9+/-3.1) months vs (12.4+/-3.6) months post the first ablation procedure, patients free of AF were 33 (78.6%) in CartoMerge group and 29 (74.4%) in CartoXP group (P>0.50). No patient suffered pulmonary vein stenosis, atrioesophageal fistula, stroke or death. CONCLUSION: Compared to CartoXP, CartoMerge shortened the catheter ablation procedure and exposure to X-ray, without affecting the clinical outcomes of circumferential pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation in experienced centres.

Multi-link Vision and MiniVision stent registry in Asian patients with coronary artery disease: a prospective, multi-center study.

BACKGROUND: Recent studies have showed that the fine mesh stents are associated with a significant reduction in both clinical and angiographic re-stenosis of the coronary arteries. To maintain a very satisfactory radio-opacity using the stents, Guidant of the USA has designed a new type of bare metal stents (BMS)-Multi-link (ML) Vision/ML MiniVision stents. The clinical outcomes of Asian patients with coronary artery disease (CAD) after implanting the Multi-link Vision or MiniVision stent were investigated in this study. METHODS: An observational, prospective, multi-center, non-randomized post marketing registry was conducted to demonstrate the efficacy of the BMS-ML Vision/ML MiniVision stents. The primary end point of the registry was clinical target lesion revascularization (TLR) at a 6-month follow-up. The major secondary end points included the rate of major adverse cardiac events (MACE) and serious adverse events (SAE) in hospital and at 6 months; and the rate of clinical TLR as a function of the type of angina. A total of 429 Asian people with 449 lesions from 14 centers were selected for this study. The average reference diameter of the lesions was (3.0 +/- 0.5) mm, and the mean length was (15.7 +/- 5.0) mm. RESULTS: The successful rate of the procedure was 99.3%. Twenty-five percent of the lesions were treated by direct stenting without pre-dilation. Eighty-six percent of the lesions were implanted with ML Vision stent. After the 6-month follow-up, the rate of clinical TLR was 1.4%. The MACE, SAE and target vessel revascularization (TVR) were 6.8%, 3.5% and 1.4% respectively. CONCLUSION: The current registry showed the excellent 6-month clinical outcomes of ML Vision/ML MiniVision stents in Asian patients with CAD.

[Metabolic syndrome complicated by peripheral arterial disease: clinical study of 2115 cases].

OBJECTIVE: To investigate the prevalence of peripheral arterial disease (PAD) complicated in metabolic syndrome (MS) and its risk factors. METHODS: The clinical data of 2115 in-patients and out-patients with MS, 1132 males and 983 females, aged 67.6 +/- 5.1 (32 approximately 91), diagnosed and treated in several hospitals in Beijing and Shanghai, were collected. The patients underwent measurement of the systolic pressures of the brachial artery and ankle artery so as to calculate the ankle-brachial index (ABI). An ABI less than 0.9 was considered to be indicative of significant PAD. The data underwent statistical analysis. RESULTS: 476 patients (22.5%) were found to have PAD, among which 246 were male aged 71.3 +/- 9.4 (51.68%) and 230 were female (48.32%) aged 71.2 +/- 8.2. The risk of PAD among then MS patients became higher along with the increase of age (OR = 1.069, 95% CI = 1.054 - 1.083), gender (OR = 1.498, 95% CI = 1.091 - 2.058), smoking status (OR = 1.763, 95% CI = 1.294 - 2.402), history of coronary heart disease, history of diabetes mellitus, and history of stroke were independently associated with low ABI (ABI < 0.9) (all P < 0.05). Higher blood urea nitrogen, creatine (CRE), and uric acid values of the female MS patients complicated by PAD was 7 mmol/L +/- 4 mmol/L, 101 mmol/L +/- 77 mmol/L, and 343 mmol/L +/- 115 mmol/L respectively, all significantly higher than those of the female MS patients not complicated by PAD (6 mmol/L +/- 4 mmol/L, 84 mmol/L +/- 70 mmol/L, and 308 mmol/L +/- 100 mmol/L respectively, P < 0.0001, P = 0.002, and P < 0.001). However, the BUN value of the male patients with MS complicated by PAD was 7.2 mmol/L +/- 4.9 mmol/L, significantly higher than that of the male MS patients nor complicated b PAD (6.5 mmol/L +/- 4.3 mmol/L, P = 0.036), however, he values of CRE and UA of the male MS patients complicated and not complicated by PAD were not significantly different (both P > 0.05), only the value of BUN of the of the male MS patients complicated by PAD was 7.2 +/- 4.9 at high risk of PAD in female patients, NOT in male patients except BUN value (P < 0.05). CONCLUSION: Patients with MS have high risk of complication by PAD, especially when they become older. Female patients with MS are more likely to have a trend towards kidney dysfunction.