Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial.

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Plasma D-dimer as a predictor of intraluminal thrombus burden and progression of abdominal aortic aneurysm.

AIM: Intraluminal thrombus (ILT) is presented in most abdominal aortic aneurysms (AAAs) and is suggested to promote AAA expansion. D-dimer, a breakdown product in the thrombus remodeling, may have prognostic value for AAA. This study investigated the interrelation between plasma D-dimer level, ILT volume, AAA size and progression. MAIN METHODS: This was a retrospective observational study that involved 181 patients with infra-renal AAA. They were divided into small and large AAA groups according to AAA diameter. 24 of them had repeated abdominal computed tomography angiography (CTA) scan and were divided into slow-growing and fast-growing AAA groups according to the median value of AAA growth rate. Baseline and follow-up plasma D-dimer level, maximum diameter of AAA, total infra-renal aortic volume and ILT volume were analyzed. KEY FINDINGS: Plasma D-dimer level was positively correlated with ILT volume (R = 0.382, P < 0.001) and maximum diameter of AAA (R = 0.442, P < 0.001). Increasing value of plasma D-dimer was positively associated with the accelerated growth rate of AAA (R = 0.720, P < 0.01). ILT volume showed positive correlation with maximum diameter (R = 0.859, P < 0.001) and growth rate of AAA (R = 0.490, P < 0.05). After adjusting the baseline ILT volume, the positive correlations remained to be statistically significant between plasma D-dimer level and AAA size (R = 0.200, P < 0.05), as well as increasing value of plasma D-dimer and growth rate of AAA (R = 0.642, P < 0.05). SIGNIFICANCE: Plasma D-dimer level reflected ILT burden in AAAs. Plasma D-dimer level and ILT volume were positively correlated with AAA size. Increasing value of plasma D-dimer and baseline ILT volume could be predictors of AAA progression.

Pharmacodynamic changes of platelet reactivity status in patients with chronic kidney disease after coronary artery stenting.

OBJECTIVES: This study was to evaluate platelet reactivity over time among patients with chronic kidney disease (CKD) receiving standard dose of clopidogrel after percutaneous coronary intervention (PCI). The effect of CYP2C19 loss-of-function genotypes on platelet reactivity was also determined. METHODS: Patients with CKD (n = 138) on maintenance dose of clopidogrel after PCI were enrolled. Platelet reactivity was assessed by measuring P2Y12 reaction units (PRU) with VerifyNow P2Y12 assay, and platelet reactivity index (PRI) with flow cytometric using vasodilator-stimulated phosphoprotein (VASP) at baseline and 2 weeks later, respectively. The genotypes of CYP2C19 were also measured concurrently. RESULTS: The proportion of patients with high platelet reactivity (HPR) ranged from 23.2% to 59.4%, and almost 1 in 5 patients had a dual conversion between HPR and non-HPR status. Patients carrying CYP2C19 loss-of-function genotypes showed a higher platelet reactivity than non-carriers, but with an undetermined HPR status between the first and second visits. The individual switch of HPR to non-HPR status existed in both loss-of-function genotype carriers and non-carriers. CONCLUSIONS: HPR conversions occur in a significant proportion of CKD patients with maintenance doses of clopidogrel treatment post-PCI, and this conversion was not confined to CYP2C19 loss-of-function genotype carriers. Risk stratification for treatment adjustment in personalized antiplatelet therapy should be investigated in future research.

IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation.

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the -2000 to -1752 bp segment of the 5'-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→︀CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the -1997 to -1700 and -1091 to -811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.

Effect of Metabolic Syndrome on Risk Stratification for Left Atrial or Left Atrial Appendage Thrombus Formation in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: Metabolic syndrome (MS) is a risk factor for stroke and thromboembolism event. Left atrial or LA appendage (LA/LAA) thrombus is a surrogate of potential stroke. The relationship between MS and atrial thrombus remains unclear. In this study, we sought to investigate the effect of MS on risk stratification of LA/LAA thrombus formation in patients with nonvalvular atrial fibrillation (NVAF). METHODS: This cross-sectional study enrolled 294 consecutive NVAF patients without prior anticoagulant and lipid-lowering therapies. LA/LAA thrombus was determined by transesophageal echocardiography. Risk assessment of LA/LAA thrombus was performed using the CHADS2 , CHA2DS2 -VASc, MS, CHADS2 -MS, and CHA2DS2 -VASc-MS scores. Logistic regression analyses were performed to determine which factors were significantly related to LA/LAA thrombus. Odds ratio (OR) including 95% confidence interval was also calculated. The predictive powers of different scores for the risk of LA/LAA thrombus were represented by C-statistics and compared by receiver operating characteristic (ROC) analysis. RESULTS: LA/LAA thrombi were identified in 56 patients (19.0%). Logistic analysis showed that MS was the strongest risk factor for LA/LAA thrombus in NVAF patients (OR = 14.698, P < 0.001). ROC curve analyses revealed that the C-statistics of CHADS2 -MS and CHA2DS2 -VASc-MS was significantly higher than those of CHADS2 and CHA2DS2 -VASc scores (CHADS2 -MS vs. CHADS2 , 0.807 vs. 0.726, P = 0.0019). Furthermore, MS was helpful for identifying individuals with a high risk of LA/LAA thrombus in the population with a low risk of stroke (CHADS2 or CHA2DS2 -VASc score = 0). CONCLUSIONS: MS is associated with LA/LAA thrombus risk in patients with NVAF. In addition to the CHADS2 and CHA2DS2 -VASc scores, the CHADS2 -MS and CHA2DS2 -VASc-MS scores provide additional information on stroke risk assessment.

Overexpression of the ß2AR gene improves function and re-endothelialization capacity of EPCs after arterial injury in nude mice.

BACKGROUND: Proliferation and migration of endothelial progenitor cells (EPCs) play important roles in restoring vascular injuries. ß2 adrenergic receptors (ß2ARs) are widely expressed in many tissues and have a beneficial impact on EPCs regulating neoangiogenesis. The aim of the present study was to determine the effect of overexpressing ß2ARs in infused peripheral blood (PB)-derived EPCs on the re-endothelialization in injured vessels. METHODS: Induction of endothelial injury was performed in male nude mice that were subjected to wire-mediated injury to the carotid artery. Human PB-derived EPCs were transfected with an adenovirus serotype 5 vector expressing ß2AR (Ad5/ß2AR-EPCs) and were examined 48 h later. ß2AR gene expression in EPCs was detected by real-time polymerase chain reaction and Western blot analysis. In vitro, the proliferation, migration, adhesion, and nitric oxide production of Ad5/ß2AR-EPCs were measured. Meanwhile, phosphorylated Akt and endothelial nitric oxide synthase (eNOS), which are downstream of ß2AR signaling, were also elevated. In an in vivo study, CM-DiI-labeled EPCs were injected intravenously into mice subjected to carotid injury. After 3 days, cells recruited to the injury sites were detected by fluorescent microscopy, and the re-endothelialization was assessed by Evans blue dye. RESULTS: In vitro, ß2AR overexpression augmented EPC proliferation, migration, and nitric oxide production and enhanced EPC adhesion to endothelial cell monolayers. In vivo, when cell tracking was used, the number of recruited CM-DiI-labeled EPCs was significantly higher in the injured zone in mice transfused with Ad5/ß2AR-EPCs compared with non-transfected EPCs. The degree of re-endothelialization was also higher in the mice transfused with Ad5/ß2AR-EPCs compared with non-transfected EPCs. We also found that the phosphorylation of Akt and eNOS was increased in Ad5/ß2AR-EPCs. Preincubation with ß2AR inhibitor (ICI118,551), Akt inhibitor (ly294002), or eNOS inhibitor (L-NAME) significantly attenuated the enhanced in vitro function and in vivo re-endothelialization capacity of EPCs induced by ß2AR overexpression. CONCLUSIONS: The present study demonstrates that ß2AR overexpression enhances EPC functions in vitro and enhances the vascular repair abilities of EPCs in vivo via the ß2AR/Akt/eNOS pathway. Upregulation of ß2AR gene expression through gene transfer may be a novel therapeutic target for endothelial repair.

Role of Circulating Fibrocytes in Cardiac Fibrosis.

OBJECTIVE: It is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis. DATA SOURCES: This review is based on the data from 1994 to present obtained from PubMed. The search terms were "circulating fibrocytes " and "cardiac fibrosis ". STUDY SELECTION: Articles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected. RESULTS: Circulating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics of hematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+). They can produce extracellular matrix and many cytokines. It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis. Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts. CONCLUSIONS: Circulating fibrocytes are effector cells in cardiac fibrosis.

Carbon Monoxide Releasing Molecule Accelerates Reendothelialization after Carotid Artery Balloon Injury in Rat.

OBJECTIVE: This study was aimed to investigate the effects of carbon monoxide releasing molecule (CORM-2), a novel carbon monoxide carrier, on the reendothelialization of carotid artery in rat endothelial denudation model. METHODS: Male rats subjected to carotid artery balloon injury were treated with CORM-2, inactive CORM-2 (iCORM-2) or dimethyl sulfoxide (DMSO). The reendothelialization capacity was evaluated by Evans Blue dye and the immunostaining with anti-CD31 antibody. The number of circulating endothelial progenitor cells (EPCs) was detected by flow cytometry. The proliferation, migration, and adhesion of human umbilical vein endothelial cells (HUVECs) were assessed by using [3H]thymidine, Boyden chamber and human fibronectin respectively. The expressions of protein were detected by using western blot analysis. RESULTS: CORM-2 remarkably accelerated the re-endothelialization 5 d later and inhibited neointima formation 28 d later. In addition, the number of peripheral EPCs significantly increased in CORM-2-treated rats than that in iCORM-2 or DMSO-treated rats after 5 d later. In vitro experiments, CORM-2 significantly enhanced the proliferation, migration and adhesion of HUVECs. The levels of Akt, eNOS phosphorylation, and NO generation in HUVECs were also much higher in CORM-2 treated group. Blocking of PI3K/Akt/eNOS signaling pathway markedly suppressed the enhanced migration and adhesion of HUVECs induced by CORM-2. CONCLUSION: CORM-2 could promote endothelial repair, and inhibit neointima formation after carotid artery balloon injury, which might be associated with the function changes of HUVECs regulated by PI3K/Akt/eNOS pathway.

Interleukin 18 and extracellular matrix metalloproteinase inducer cross-regulation: implications in acute myocardial infarction.

Circulating interleukin-18 (IL-18) is thought to promote atherosclerosis and cardiovascular complications such as plaque rupture. Atherosclerosis is also characterized by smooth muscle cell migration, a consequence of extracellular matrix (ECM) degradation regulated by metalloproteinases (MMPs). Because extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote plaque instability by inducing ECM degradation and MMP synthesis, we investigated whether a cross-regulatory interaction exists between IL-18 and EMMPRIN in human monocytes. EMMPRIN levels in monocytes were markedly greater in 20 patients with acute myocardial infarction (AMI) compared with 20 patients with stable angina pectoris or 20 healthy volunteers (control group). The levels of IL-18 and MMP-9 in serum were also significantly greater in the AMI group in comparison with the other 2 groups. IL-18 levels positively correlated with increased levels of EMMPRIN in monocytes. In vitro, the expression of EMMPRIN was increased in monocytes cultured with IL-18, and IL-18 secretion was augmented in monocytes cultured with EMMPRIN. Gene silencing of EMMPRIN by small interfering RNA reduced monocyte secretion of both IL-18 and MMP-9. In the present study, cross-regulation between IL-18 and EMMPRIN in monocytes was demonstrated. This interaction may amplify the inflammatory cascade and be responsible for increased monocytic MMP-9 serum levels in atherosclerosis, contributing to atherosclerotic plaque destabilization and subsequent AMI.

[Impact of insulin resistance on prognosis in non-diabetic patients with acute coronary syndromes].

OBJECTIVE: To evaluate the impact of insulin resistance (IR) on prognosis in non-diabetic acute coronary syndrome patients. METHODS: In this prospective study, we enrolled 332 non-diabetic patients suffering from acute coronary syndrome. The patients were divided into three groups by HOMA-IR which calculated by formula: low HOMA-IR group (HOMA-IR < 2), 44 cases; moderate HOMA-IR group (2 ≤ HOMA2-IR < 6), 99 cases; high HOMA-IR group (HOMA ≥ 6) with HOMA index, 179 cases. The in-hospital medical records of patients were compared, and all patients were followed up for one year after discharge. RESULTS: Incidence of hypertension (P = 0.013), dyslipidemia (P < 0.001), faster resting heart rate (P < 0.001) and number of triple vessel coronary artery disease (P = 0.017) in high HOMA-IR group were significantly higher than in low and moderate HOMA-IR group. During follow-up, the major end-point events increased in proportion to IR grade: 64.3% (26/44) in the high HOMA-IR group, 54.7% (52/99) in moderate HOMA-IR group and 41.3% (74/199) in low HOMA-IR group (P = 0.034). Multivariable logistic regression analysis showed that high sensitivity C reactive protein (OR = 1.012, 95%CI:1.002-1.022, P = 0.022), HOMA-IR (OR = 1.250, 95%CI:1.043-1.497, P = 0.015) , triple vessel coronary artery disease (OR = 5.914, 95%CI:2.947-11.868, P < 0.001) , ischemic changes on ECG (OR = 5.495, 95%CI:2.925-10.324, P < 0.001) and low left ventricular ejection fraction (LVEF ≤ 40%) (OR = 13.205, 95%CI:5.000-34.661, P < 0.001) were independent risk factor for major end-point events during follow-up. CONCLUSIONS: Increased insulin resistance is linked with poor prognosis of non-diabetic patients with acute coronary syndrome.

Triple antithrombotic therapy versus double antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients requiring chronic oral anticoagulation: a meta-analysis.

BACKGROUND: Whether an addition of OAC to double antiplatelet therapy for patients with an indication of chronic oral anticoagulation undergoing PCI-S may improve clinical outcomes is still debated. This meta-analysis aimed to update and re-compare the benefits and risks of triple antithrombotic therapy (TT) with double anti-platelet therapy (DAPT) after in patients who requiring oral anticoagulation after percutaneous coronary interventions with stenting (PCI-s). METHODS: Ten reports of observational retrospective or prospective studies were retrieved, including a total of 6296 patients, follow-up period ranging from 1 year to 2 years. RESULTS: Baseline characteristics were similar in both groups. The main finding of this study is the overall incidence of major adverse cardiovascular events (MACE), myocardial infarction (MI) and stent thrombosis was comparable between two groups. Patients with TT was associated with significant reduction in ischemic stroke (OR: 0.27; 95%CI: 0.13 - 0.57; P = 0.0006) as compared to DAPT. We reaffirmed triple therapy significantly increased the risk of major bleeding (OR: 1.47; 95%CI: 1.22 - 1.78; P < 0.0001) and minor bleeding (OR: 1.55; 95%CI: 1.07 - 2.24; P = 0.02). CONCLUSIONS: Triple therapy is more efficacious in reducing the occurrence of ischemic stroke in PCI-s patients with an indication of chronic oral anticoagulation (OAC), compared with DAPT. However, it significantly increased major and minor risk of bleeding. It is imperative that further prospective randomized controlled trials are required to defne the best therapeutic strategy for patients with an indication of chronic OAC undergoing PCI-s.

Optimal strategy of coronary revascularization in chronic kidney disease patients: a meta-analysis.

BACKGROUND: Patients with chronic kidney disease (CKD) have high risks of coronary artery disease (CAD). Coronary revascularization is beneficial for long-term survival, but the optimal strategy remains still controversial. METHODS: We searched studies that have compared percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) for revascularization of the coronary arteries in CKD patients. Short-term (30 days or in-hospital) mortality, long-term (at least 12 months) all-cause mortality, cardiac mortality and the incidence of late myocardial infarction and recurrence of revascularization were estimated. RESULTS: 28 studies with 38,740 patients were included. All were retrospective studies from 1977 to 2012. Meta-analysis showed that PCI group had lower short-term mortality (OR 0.55, 95% CI 0.41 to 0.73, P<0.01), but had higher long-term all-cause mortality (OR 1.29, 95% CI 1.23 to 1.35, P<0.01). Higher cardiac mortality (OR 1.08, 95% CI 1.01 to 1.15, P<0.05), higher incidence of late myocardial infarction (OR 1.78, 95% CI 1.65 to 1.91, P<0.01) and recurring revascularization rate (OR 2.94, 95%CI 2.15 to 4.01, P<0.01) is found amongst PCI treated patients compared to CABG group. CONCLUSIONS: CKD patients with CAD received CABG had higher risk of short-term mortality but lower risks of long-term all-cause mortality, cardiac mortality and late myocardial infarction compared to PCI. This could be due to less probable repeated revascularization.

Bare-metal stent versus drug-eluting stent in large coronary arteries: meta-analysis of randomized controlled trials.

BACKGROUND: Uncertainties exist with regard to the efficacy of drug-eluting stent (DES) versus bare-metal stent (BMS) in large coronary arteries. OBJECTIVE AND METHODS: The aim of this study was to investigate the efficacy of BMS versus DES in terms of clinical events in large coronary vessels (≥3.0 mm) by performing a meta-analysis of all relevant randomized controlled trials (RCTs). RESULTS: Six RCTs with 4,399 patients were included in this study. Overall, there were no significant between-group differences in the risks of the composite of cardiac death and nonfatal myocardial infarction (cardiac death/MI), cardiac death, myocardial infarction, and stent thrombosis, however, DES was associated with significant reduction in the risk of target vessel revascularization (TVR) compared with BMS [0.48 (0.33, 0.70)] with consistent benefits among patients with reference vessel diameter ≥ 3.5 mm, reference vessel diameter ≥ 4.0 mm, stent length ≤ 15 mm, first-generation DES or second-generation DES. In patients with ≥ 3-year follow-up, there were no significant between-group differences in the risk of cardiac death/MI, TVR, cardiac death, myocardial infarction or stent thrombosis. CONCLUSIONS: This meta-analysis suggests that DES is superior to BMS in terms of adverse cardiac events in large coronary arteries at the mid-term follow-up. The long-term efficacy of newer-generation DES versus BMS in larger coronary arteries is still worth further evaluation.

Poor coronary collateral vessel development in patients with mild to moderate renal insufficiency.

BACKGROUND: The development of coronary collaterals is crucial to survival through acute ischemia. Mild to moderate loss of renal function has been suggested to play a role in this event, but evidential data are scarce. The aim of this study was to investigate the relationship between mild to moderate renal insufficiency and coronary collateral development in patients with chronic total coronary artery occlusion. METHODS AND RESULTS: A total of 83 patients with mild to moderate loss of renal function (30 mL/min/1.73 m(2) ≤ eGFR < 90 mL/min/1.73 m(2)) with chronic total coronary artery occlusion were included in our study. The collateral circulation was graded according to Rentrop classification and the function of collateral circulation was graded according to Werner collateral connection (CC) grades. Compared to patients with good collateral circulation (Rentrop = 2,3), eGFR was found to be lower in those patients with poor coronary collateral circulation (Rentrop = 0,1) (63.30 ± 10.51 vs. 54.13 ± 10.56, P = 0.02). eGFR was also found to be lower in poorly functioning coronary collateral circulation (CC = 0,1) than in efficiently functioning coronary collateral circulation (CC = 2) (55.22 ± 9.98 vs. 66.28 ± 9.16, P = 0.03). Multiple logistic regression analysis showed that low eGFR was independently associated with poor coronary collateral circulation (Rentrop = 0,1, 95% CI, 0.09-1.09, P = 0.044) and poor function of coronary collateral circulation (CC = 0,1, 95% CI, 0.02-0.17, P = 0.02). CONCLUSIONS: Lower eGFR is associated with poorer coronary collateral vessel development in patients experiencing mild to moderate renal insufficiency. Moreover, eGFR represents an independent factor affecting coronary collateral vessel development.

Pivotal role of inflammation in vascular endothelial dysfunction of hyperlipidemic rabbit and effects by atorvastatin.

AIMS: To evaluate the role of inflammation in vascular endothelial function of hyperlipidemic rabbits and atorvastatin's effects on it. METHODS: 22 rabbits were divided into high-fat diet and atorvastatin plus high-fat diet group. Basic levels of total and low-density lipoprotein cholesterol, triglyceride, C-reactive protein (CRP), interleukin-6 (IL-6), nitric oxide (NO), endothelin-1 (ET-1), fasting blood glucose (FBG), insulin and endothelial function were measured when grouping. Eight weeks later, all above parameters were remeasured and repeated again at days 1, 4 and 7 after atorvastatin withdrawal. RESULTS: Eight-week high-fat diet could not cause the changes of FBG and insulin, but significantly induce increased blood lipids as well as inflammatory markers, imbalance between ET-1 and NO, and direct endothelial dysfunction, which could be significantly improved by atorvastatin therapy but could not be well controlled to near baseline. Abrupt withdrawal of atorvastatin caused sharp increase of inflammatory markers and endothelial dysfunction at days 4 and 7 after atorvastatin withdrawal independent of the changes of blood lipids. CONCLUSIONS: High-fat diet could cause endothelial dysfunction associated with inflammation, and atorvastatin could counter-regulate it. Sudden withdrawal of statins could induce rebound of inflammatory response and endothelial dysfunction independent of changes of lipids, which may be responsible for increased cardiovascular events in patients with coronary artery disease after withdrawing statins.

Increased expression of granulocyte colony-stimulating factor mediates mesenchymal stem cells recruitment after vascular injury.

BACKGROUND: Recent studies indicate that bone marrow-derived cells may significantly contribute to atherosclerosis, post-angioplasty restenosis and transplantation-associated vasculopathy. The responsible bone marrow (BM) cells and mechanisms regulating the mobilization of these cells are currently unclear. The purpose of this study was to investigate the expression of granulocyte colony-stimulating factor (G-CSF) on injured arteries and its effects on mesenchymal stem cells (MSCs) differentiation into vascular smooth muscle cells (VSMCs) in the process of vascular remodeling. METHODS: Balloon-mediated vascular injury was established in female rats (n = 100) which received radioprotective whole female BM cells by tail vein injection and male MSCs through a tibial BM injection after lethal irradiation. The injured and contralateral carotid arteries were harvested at 3, 7, 14 and 28 days after treatment. RESULTS: Morphometric analysis indicated that intima to media area-ratio (I/M ratio) significantly increased at 28 days, 0.899 ± 0.057 (P < 0.01), compared with uninjured arteries. Combining fluorescence in situ hybridization (FISH) and immunohistochemical analysis showed that a significant number of the neointimal cells derived from MSCs, (45.2 ± 8.5)% at 28 days (P = 0.01), compared with (23.5 ± 6.3)% at 14 days. G-CSF was induced in carotid arteries subject to balloon angioplasty (fold mRNA change = 8.67 ± 0.63 at three days, relative G-CSF protein = 0.657 ± 0.011 at three days, P < 0.01, respectively, compared with uninjured arteries). G-CSF was chemotactic for MSCs but did not affect the differentiation of MSCs into smooth-muscle-like cells. CONCLUSION: Increased expression of G-CSF by injured arteries plays an essential role in contribution to recruitment and homing of MSCs to the site of the arterial lesion.

[The expression and significance of activator protein-1 and matrix metalloproteinases in the human heart post acute myocardial infarction].

OBJECTIVE: To investigate the expression and significance of activator protein-1 (AP-1) and matrix metalloproteinases (MMPs) in acute myocardial infarction (AMI) subjects. METHODS: Immunohistochemical techniques were used to detect the subunit of AP-1 (c-Jun), MMP-2 and MMP-9 in human AMI and normal heart tissue and the expressions of c-Jun and MMPs were measured with computer image analysis system. RESULTS: (1) There were expressions of c-Jun, MMP-2 and MMP-9 in normal heart tissue, mainly in myocardial cells and cardiac fibroblasts, and their expressions in AMI myocardial tissues were all significantly higher than those in normal myocardial tissues (P < 0.05). (2) The level of MMP-9 expression was significantly and positively correlated with c-Jun in AMI heart tissue (r = 0.773, P < 0.01). CONCLUSIONS: The expressions of AP-1 and MMPs increase in human myocardial infarction. These findings suggest that AP-1 transcription activation pathway and MMPs may play an important role in ventricular remodeling of myocardial infarction.

[Clinical analysis of inappropriate shock of implantable cardioverter defibrillators].

OBJECTIVE: Implantable cardioverter defibrillator (ICD) can effectively treat life-threatening ventricular arrhythmias. The most common side effect is inappropriate discharge. This study analyzes the incidence and causes of inappropriate discharges of ICD in our hospital. METHODS: Forty-three patients implanted with ICD in our hospital from November 2001 to October 2007 were involved in our study. Patients were followed-up regularly. All episodes recorded and stored in the ICD were analyzed. RESULTS: Seven of the 43 patients underwent ninety-six inappropriate discharges. Inappropriate discharges in six patients were caused by supraventricular tachyarrhythmias (SVT). In one patient the discharge was caused by noise. Most inappropriate discharges occurred in the first year after implantation. The history of atrial fibrillation before implantation is an independent predictor of inappropriate discharges. CONCLUSIONS: The incidence of inappropriate discharge is 16.3% in our study and the most common cause is SVT. Most inappropriate discharges occur in the first year after implantation. Patients with atrial fibrillation history have a higher risk of inappropriate discharges.

[PPAR gamma agonist rosiglitazone alleviates hypoxia/reoxygenation-induced oxidative stress and apoptosis in rat cardiac myocytes].

OBJECTIVE: To observe the effects of different concentrations of PPAR gamma agonist rosiglitazone on hypoxia/reoxygenation-induced oxidative stress, cell viability and apoptosis in rat cardiac myocytes. METHODS: Cultured rat cardiac myocytes were divided into 5 groups, namely group I (normal group), group II (20 micromo/L ROS group), group III (I/R group), group IV (I/R+20 micromo/L ROS group), and group V (I/R+80 micromo/L ROS group). Group IV and group V were treated with rosiglitazone 12 h before hypoxia/reoxygenation. The changes in cell morphology were observed under optical and transmission electron microscopy, and levels of malondialdehyde (MDA), superoxide dismutase (SOD) activity, and lactate dehydrogenase (LDH) content were determined after the treatment. MTT assay was performed to assess the cell viability and flow cytometry was used to analyze the cell apoptosis. RESULTS: Hypoxia/reoxygenation resulted in significantly increased MDA and LDH contents and apoptosis of the cardiac myocytes (P<0.05), but lowered SOD activity and the cell viability (P<0.05). The MDA and LDH contents and apoptotic rate were significantly lower but SOD content and cell vitality significantly higher in groups IV and V than in group III (P<0.05). Group V showed significantly lower MDA and LDH contents and apoptotic rate but higher but SOD content and cell vitality than group IV (P<0.05). Electron microscopy revealed obvious apoptotic changes in group III, and only mild changes were found in group V. CONCLUSION: Rosiglitazone can significantly reduce hypoxia/reoxygenation-induced oxidative stress in cardiac myocytes, improve the cell viability and dose-dependently reduce the apoptotic rate of the cardiac myocytes.