Background-Coronary stenting is associated with a restenosis rate of 15% to 20% at 6-month follow-up, despite optimum angiographic stent implantation. In this multicenter registry, we investigated the relation between optimum physiological stent implantation as assessed by poststent fractional flow reserve (FFR) and outcome at 6 months. Methods and Results-In 750 patients, coronary pressure measurement at maximum hyperemia was performed after angiographically apparently satisfactory stent implantation. Poststenting FFR was calculated and related to major adverse events (including need for repeat target vessel revascularization) at 6 months. In 76 patients (10.2%), at least 1 adverse event occurred. Five patients died, 19 experienced myocardial infarction, and 52 underwent at least 1 repeat target vessel revascularization. By multivariate analysis, FFR immediately after stenting was the most significant independent variable related to all types of events. In 36% of the patients, FFR normalized (Ͼ0.95), and event rate was 4.9% in that group. In 32% of the patients, poststent FFR was between 0.90 and 0.95, and event rate was 6.2%. In 32% of patients, poststent FFR was Ͻ0.90, and event rate was 20.3%. In 6% of the patients, FFR was Ͻ0.80, and event rate was 29.5% (PϽ0.001). Conclusions-FFR after stenting is a strong independent predictor of outcome at 6 months.

We hypothesized that a small molecule CXCR4 antagonist, AMD3100 (AMD), could augment the mobilization of bone marrow (BM)-derived endothelial progenitor cells (EPCs), thereby enhancing neovascularization and functional recovery after myocardial infarction. Single-dose AMD injection administered after the onset of myocardial infarction increased circulating EPC counts and myocardial vascularity, reduced fibrosis, and improved cardiac function and survival. In mice transplanted with traceable BM cells, AMD increased BM-derived cell incorporation in the ischemic border zone. In contrast, continuous infusion of AMD, although increasing EPCs in the circulation, worsened outcome by blocking EPC incorporation. In addition to its effects as a CXCR4 antagonist, AMD also up-regulated VEGF and matrix metalloproteinase 9 (MMP-9) expression, and the benefits of AMD were not observed in the absence of MMP-9 expression in the BM. These findings suggest that AMD3100 preserves cardiac function after myocardial infarction by enhancing BM-EPC-mediated neovascularization, and that these benefits require MMP-9 expression in the BM, but not in the ischemic region. Our results indicate that AMD3100 could be a potentially useful therapy for the treatment of myocardial infarction.angiogenesis | stem cell | vasculogenesis

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The incidence of coronary abnormalities is relatively low in patients with Takayasu arteritis; however, surgical treatment is recommended for patients with coronary ostial stenoses because coronary ischemia can be one of the major causes of death.

There is a low incidence of SCD in survivors of MI in the primary PCI era, although LVEF is a predictor of increased risk for SCD.

Aims HMG-CoA reductase inhibitors (statins) have been demonstrated to have in vitro vascular effects. The aim of this study was to determine whether statins actually have in vivo vascular effects independent of their cholesterol-lowering effect. Methods We investigated the effect of a single dose of cerivastatin on vascular endothelial function by measuring flow-mediated dilatation of the brachial artery on ultrasound in 30 healthy volunteers with normal serum cholesterol concentrations. They were randomized to either placebo group ( n = 15) or cerivastatin group ( n = 15), and flow-mediated dilatation and endothelium-dependent dilatation were evaluated at before and 1 h, 3 h, 6 h, and 12 h after administration of placebo or cerivastatin. Results There were no differences in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde-LDL, and high-sensitivity C-reactive protein before and after administration of placebo or cerivastatin. Cerivastatin significantly increased flow-mediated dilatation at 3 h ( P < 0.001), and this increase rapidly returned to the baseline level 6 h after administration. Endotheliumindependent dilatation of brachial artery was not altered. Conclusions A single dose of cerivastatin increased vascular endothelial responsiveness. Our data suggest that cerivastatin has a direct effect on the blood vessels that is independent of its lipid-lowering effect, and thus can be considered as a vascular statin.

Background CXC-chemokine receptor 4 (CXCR4) regulates the retention of stem/progenitor cells in the bone marrow (BM), and the CXCR4 antagonist AMD3100 improves recovery from coronary-ligation injury by mobilizing stem/progenitor cells from the BM to the peripheral blood. Thus, we investigated whether AMD3100 also improves recovery from ischemia-reperfusion (IR) injury, which more closely mimics myocardial infarction in patients, because blood flow is only temporarily obstructed. Methods and Results Mice were treated with single subcutaneous injections of AMD3100 (5 mg/kg) or saline after IR injury. Three days later, histological measurements of the infarct-area/area-at-risk ratio were smaller in AMD3100-treated mice than in mice administered saline, and echocardiographic measurements of left-ventricular function were greater in the AMD3100-treated mice at week 4. CXCR4+ cells were mobilized for just 1 day in both groups, but the mobilization of sca1+/flk1+ cells endured for 7days in AMD3100-treated mice compared to just 1 day in the saline-treated mice. AMD3100 upregulated BM levels of endothelial nitric oxide synthase (eNOS) and two targets of eNOS signaling, matrix-metalloproteinase 9 and soluble Kit ligand. Furthermore, the loss of BM eNOS expression abolished the benefit of AMD3100 on sca1+/flk1+ cell mobilization without altering the mobilization of CXCR4+ cells, and the cardioprotective effects of AMD3100 were retained in eNOS-knockout mice that had been transplanted with BM from wild-type mice, but not in wild-type mice with eNOS-knockout BM. Conclusions AMD3100 prolongs BM progenitor mobilization and improves recovery from IR injury, and these benefits appear to occur through a previously unidentified link between AMD3100 and BM eNOS expression.

Obstructive sleep apnea (OSA), characterized by partial or complete occlusion of the pharynx during sleep, results in persistent inspiratory effort and interruption of airflow. During each episode of apnea, OSA patients develop increased transmural pressure in the aortic wall. Accordingly, to test the hypothesis that the presence of OSA would be associated with greater thoracic aortic size, we prospectively assessed 150 consecutive patients, newly referred to the sleep clinic in our institution, in a crosssectional study to confirm OSA. The patients underwent sleep study and chest computed tomography (CT)-derived thoracic aortic diameter. In this particular period, a chest CT was performed within 3 months of the sleep study upon informed consent to our protocol. Exclusion criteria included: 1) prior history of aortic dissection, aortic valvular disease, and clinical characteristics of Marfan's syndrome; 2) central sleep apnea; 3) treatment for sleep apnea; and 4) dialysis. The outer diameter of the ascending aorta was measured by caliper within the CT image. Overnight sleep study was performed using cardiopulmonary monitoring (Morpheus, Teijin Inc., Tokyo, Japan). The apnea-hypopnea index (AHI) was quantified as the frequency of apneas and hypopneas per hour of bed time. OSA was defined as AHI Ն10/h. The data are presented as mean Ϯ SD or frequencies. To determine the independent factors, the multiple linear regression model with backward elimination technique was used, including older age, male gender, blood pressure, hypertension, dyslipidemia, diabetes mellitus, ischemic heart disease, smoking, and AHI. Comparisons between the 2 groups were performed by Student t test for the unadjusted aortic diameter and by analysis of covariance for the adjusted aortic diameter.The patients' mean age was 60 Ϯ 11 years; 125 (83%) were men, with mean body mass index of 24.7 Ϯ 3.1 kg/m 2 . Fifty-nine percent of patients had hypertension. At assessment, 91% of patients had already taken prescribed antihypertensive medications. One hundred ten patients (73%) had OSA. On univariate analysis, older age, male gender, body mass index, systolic blood pressure, pulse pressure, hypertension, dyslipidemia, ischemic heart disease, and AHI were positively correlated with thoracic aortic size. On multivariate analysis, older age (per 10-year increase, coefficient 1.82, 95% confidence interval [CI]: 1.13 to 2.34, p Ͻ 0.001), male gender (coefficient 3.25, 95% CI: 1.63 to 4.87, p Ͻ 0.001), and AHI (per 10-event/h increase, coefficient 0.62, 95% CI: 0.25 to 0.98, p Ͻ 0.001) remained as factors associated with greater thoracic aortic diameter. Contrarily, there was no significant independent relationship between blood pressure/hypertension and thoracic aortic size. Additionally, patients with OSA had a significantly greater thoracic aortic size than those without OSA (p Ͻ 0.001) (Fig. 1), even if adjusted for older age and male gender (p Ͻ 0.001).Increased thoracic aortic size is known to be related to aging, male, genetic mutation including M...