Background-Endothelial progenitor cells (EPCs) circulate in adult peripheral blood (PB) and contribute to neovascularization. However, little is known regarding whether EPCs and their putative precursor, CD34-positive mononuclear cells (MNC CD34ϩ ), are mobilized into PB in acute ischemic events in humans. Methods and Results-Flow cytometry revealed that circulating MNC CD34ϩ counts significantly increased in patients with acute myocardial infarction (nϭ16), peaking on day 7 after onset, whereas they were unchanged in control subjects (nϭ8) who had no evidence of cardiac ischemia. During culture, PB-MNCs formed multiple cell clusters, and EPC-like attaching cells with endothelial cell lineage markers (CD31, vascular endothelial cadherin, and kinase insert domain receptor) sprouted from clusters. In patients with acute myocardial infarction, more cell clusters and EPCs developed from cultured PB-MNCs obtained on day 7 than those on day 1. Plasma levels of vascular endothelial growth factor significantly increased, peaking on day 7, and they positively correlated with circulating MNC CD34ϩ counts (rϭ0.35, Pϭ0.01). Conclusions-This is the first clinical demonstration showing that lineage-committed EPCs and MNCCD34ϩ , their putative precursors, are mobilized during an acute ischemic event in humans.

Background-Endothelium-derived nitric oxide (EDNO) plays an important role in the regulation of angiogenesis, whereas hypercholesterolemia (HC) impairs EDNO release. We examined the hypothesis that HC may inhibit ischemia-induced angiogenesis by inhibition of EDNO in a rat model of unilateral hindlimb ischemia and that oral L-arginine supplementation, a substrate for NO synthase, may prevent HC-related impairment of angiogenesis. Methods and Results-Male Sprague-Dawley rats were fed (A) standard diet (control), (B) 2% high-cholesterol diet (HC group), or (C) high-cholesterol diet with oral L-arginine (2.25% in drinking water) (HCϩL-arg group). At 2 weeks of the dietary intervention, unilateral limb ischemia was surgically induced in all animals. Dietary HC groups (B and C) revealed elevated total and LDL cholesterol levels compared with control animals. Laser Doppler blood flow analyses showed significant decreases in the ischemic/normal limb blood flow ratio in the HC group compared with controls (PϽ0.05) when followed up until 4 weeks after surgery. Selective angiography and immunohistochemical analyses in the ischemic limb at postoperative day 14 revealed significantly lower angiographic scores (PϽ0.01) and capillary densities (PϽ0.01) in the HC group than controls, which were associated with decreased tissue contents of NO x and cGMP. Oral L-arginine supplementation (HCϩL-arg) significantly improved all parameters of the laser Doppler blood perfusion ratio, angiographic scores, and capillary densities (PϽ0.01 versus HC group), which were accompanied by significant elevations in serum L-arginine levels and tissue NO x and cGMP contents. Conclusions-Collateral vessel formation and angiogenesis in response to hindlimb ischemia were significantly attenuated in rats with dietary HC. The mechanism may be related to the reduced NO bioactivity in the ischemic tissues. Augmentation of the tissue NO activity by oral L-arginine supplementation restored the impaired angiogenesis in HC. (Circulation. 2000;102[suppl III]:III-370-III-376.)

Summary: Three dimensional (3D) nanostructures of particulate silicas in natural rubber (NR) were observed for the first time by use of 3D transmission electron microscopy (3D‐TEM) combined with electron tomography. The method enabled us to visualize and evaluate structural characteristics in 3D space, such as the size and the volume of in situ silica generated in the NR matrix by the sol‐gel reaction of tetraethoxysilane, at nanometer scale resolution.The reconstructed mass density view of the silica in an in situ silica‐filled natural rubber vulcanizate, as determined by 3D‐TEM.imageThe reconstructed mass density view of the silica in an in situ silica‐filled natural rubber vulcanizate, as determined by 3D‐TEM.

The present findings suggest that CCR is a promising strategy for prevention and treatment of sarcopenia in patients with CVD.

During the long-term follow-up of the Japanese form of apical hypertrophy, giant negative T waves disappeared in association with decreases in R wave amplitude in lead V5, indicating that these ECG hallmarks are clinical features that evolve progressively during the natural course of the disease.

BackgroundSarcopenia is an aging and disease-related syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, with the risk of frailty and poor quality of life. Sarcopenia is diagnosed by a decrease in skeletal muscle index (SMI) and reduction of either handgrip strength or gait speed. However, measurement of SMI is difficult for general physicians because it requires special equipment for bioelectrical impedance assay or dual-energy X-ray absorptiometry. The purpose of this study was, therefore, to explore a novel, simple diagnostic method of sarcopenia evaluation in patients with cardiovascular diseases (CVD).MethodsWe retrospectively investigated 132 inpatients with CVD (age: 72±12 years, age range: 27–93 years, males: 61%) Binomial logistic regression and correlation analyses were used to assess the associations of sarcopenia with simple physical data and biomarkers, including muscle-related inflammation makers and nutritional markers.ResultsSarcopenia was present in 29.5% of the study population. Serum concentrations of adiponectin and sialic acid were significantly higher in sarcopenic than non-sarcopenic CVD patients. Stepwise multivariate binomial logistic regression analysis revealed that adiponectin, sialic acid, sex, age, and body mass index were independent factors for sarcopenia detection. Sarcopenia index, obtained from the diagnostic regression formula for sarcopenia detection including the five independent factors, indicated a high accuracy in ROC curve analysis (sensitivity 94.9%, specificity 69.9%) and the cutoff value for sarcopenia detection was -1.6134. Sarcopenia index had a significant correlation with the conventional diagnostic parameters of sarcopenia.ConclusionsOur new sarcopenia index using simple parameters would be useful for diagnosing sarcopenia in CVD patients.

Abstract-Platelet aggregation is inhibited through a negative feedback mechanism by the L-arginine/nitric oxide (NO) pathway found in platelets themselves. We have shown that long-term smoking impairs the bioactivity of platelet-derived NO (PDNO), resulting in an increased platelet aggregability. However, little is known about the relation between other coronary risk factors and PDNO release. Accordingly, this study was undertaken to examine whether other coronary risk factors are related to the impairment of PDNO bioactivity. We measured collagen-induced PDNO release with an NO-selective electrode in 61 subjects (mean age 47 years, range 24 to 74 years) who underwent complete physical and laboratory examinations. There was a significant inverse correlation between PDNO release and the number of coronary risk factors (rϭϪ0. Key Words: platelets Ⅲ nitric oxide Ⅲ risk factors Ⅲ atherothrombosis P latelets possess the functional L-arginine/nitric oxide (NO) pathway via constitutive NO synthase. 1,2 Platelet-derived NO (PDNO) increases the intraplatelet level of cGMP and inhibits platelet aggregation. 1 This modulation of platelet aggregation via the L-arginine/NO pathway is recognized as a negative-feedback mechanism to inhibit aggregation. 3,4 Using an NO-selective electrode, we 5 and others 6 directly measured PDNO release during platelet aggregation, which was potentiated by L-arginine and attenuated by inhibitors of NO synthase, indicating the existence of an L-arginine/NO pathway in human platelets. 1,7 PDNO has been shown to play a functional role in the inhibition of not only platelet activation but also platelet recruitment after aggregation. 8 Recently, we have shown that long-term smoking impairs PDNO release, resulting in an increased platelet aggregability. 5 However, little is known about the relation between other coronary risk factors and PDNO release. Accordingly, the present study was undertaken to investigate the hypothesis that other coronary risk factors impair platelet function and thereby affect PDNO release in subjects with major risk factors. Methods Study SubjectsThe study population consisted of 61 subjects who agreed to participate in the study. The subjects underwent complete routine physical and laboratory examinations, and their complete anamnesis was obtained. Of the 61 subjects, 42 were healthy volunteers, 12 had stable effort angina, and 7 had previous myocardial infarction. Medications, including long-acting nitrates, calcium channel blockers, ␤-blockers, and ACE inhibitors, were withheld for Ն24 hours, and aspirin was withheld for Ն1 week before the study. None of the patients had received cholesterol-lowering agents. Patients with acute coronary syndromes, valvular heart diseases, or heart failure were excluded from the study. The present protocol was approved by our institutional ethic committee, and informed consent for the study was obtained from all patients. Definition of Coronary Risk FactorsCoronary risk factors in this study were determined according to the Sixth Report o...

Background-Hypercholesterolemia enhances platelet aggregability. Statins have beneficial effects on cardiovascular events. The purpose of this study is to investigate whether statins inhibit platelet aggregation and, if so, the mechanisms. Methods and Results-Twelve patients with hypercholesterolemia were prospectively randomized in a crossover design to receive either fluvastatin (20 mg/d) or colestimide (3000 mg/d) for 12 weeks. The subjects were switched to the opposite arm for additional 12 weeks. Before and after first and second treatments, experiments were performed. Eleven age-matched volunteers with normal lipid profiles served as controls. ADP-induced platelet aggregation, platelet-derive nitric oxide (PDNO) release, intraplatelet levels of GSH and GSSG, and intraplatelet nitrotyrosine production during platelet aggregation were measured. Fluvastatin and colestimide equally lowered total and low density lipoprotein cholesterol levels in hypercholesterolemia. Platelet aggregation was greater in hypercholesterolemia than in normocholesterolemia before treatment and was altered by fluvastatin. PDNO release, intraplatelet glutathione level, and GSH/GSSG ratio were lower in hypercholesterolemia than in normocholesterolemia before treatment and were increased by fluvastatin. Intraplatelet nitrotyrosine formation was greater in hypercholesterolemia than in normocholesterolemia, and decreased by fluvastatin. Colestimide did not have such effects. In vitro application of fluvastatin dose-dependently inhibited platelet aggregation. Furthermore, in vitro application of fluvastatin dose-dependently inhibited platelet nitrotyrosine expressions and the inhibitory effects by fluvastatin were reversed by preincubation with geranylgeranylpyrophosphate. Conclusions-Fluvastatin altered platelet aggregability in hypercholesterolemic patients in a cholesterol-lowering independent manner, which was partly mediated by the improvement of intraplatelet redox imbalance. (Arterioscler