Physical assignment of markers, SJ017, SJ042, and SJ065 to swine chromosome X.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
H Yasue
Publications and source records attributed to H Yasue.
Genetic risk factors for coronary artery spasm: significance of endothelial nitric oxide synthase gene T-786-->C and missense Glu298Asp variants.
BACKGROUND: We recently identified two endothelial nitric oxide synthase (eNOS) gene polymorphisms, Glu298Asp and T-786-->C, which are independently associated with coronary spasm. eNOS gene intron 4b/a polymorphism is also reported to be involved in smoking-dependent coronary artery disease. The genetic linkage among these polymorphisms remains unknown. Also, it is unclear which variant is most responsible for coronary spasm. In the present study, we first examined the genetic linkage among these three variants. Next, we studied the risk factors of coronary spasm by using all significant genetic and conventional risk factors in a large-scale study. METHODS: The genotype and allele frequencies for the T-786-->C, intron 4b/a, and Glu298Asp variants were assessed in 423 randomly selected DNA samples to examine their genetic linkages. The relative capacities of all risk factors to predict coronary spasm were then analyzed using multiple logistic regression in 201 patients with coronary spasm and 345 volunteers. RESULTS: Comparison of allele frequencies revealed that the eNOS intron 4a allele was significantly linked to the T-786-->C mutation (P < 0.00001), whereas there was not a linkage between the intron 4a allele and the Glu298Asp variant (P = 0.1437) or between the Glu298Asp variant and the T-786-->C mutation (P = 0.1996). Multiple logistic regression revealed that the most predictive independent risk factor for coronary spasm was the T-786-->C mutation (P < 0.001), followed by cigarette smoking (P < 0.001), hypertension (P = 0.004), and the Glu298Asp variant (P = 0.028). CONCLUSIONS: We found that the T-786-->C mutation and the intron 4a allele are in linkage disequilibrium. We previously showed that the T-786-->C mutation reduced eNOS gene promoter activity. In that context, our results strongly suggest that the T-786-->C mutation underlies the functional characteristics of the intron 4a allele. Further, multiple logistic regression analysis revealed that the T-786-->C mutation is the most predictive risk factor for coronary spasm, followed by cigarette smoking. Given that those effects are potentially additive, patients carrying the eNOS gene variants should be strongly cautioned against smoking.
Adult↗
Expression of five steroidogenic genes including aromatase gene at early developmental stages of chicken male and female embryos.
In the course of avian embryo development, estrogen has been indicated to play a key role in gonadal differentiation by the inhibition of aromatase (P-450arom) that synthesizes estrogen from androgen. Biosynthesis of estrogen requires not only P-450arom but also other enzymes for a steroidogenic pathway. To elucidate gonadal differentiation, the steroidogenic pathway should be studied comprehensively in the early developmental stages including that of sex differentiation. Therefore, in the present study, the expressions of the steroidogenic genes, P-450scc, 3beta-HSD, P-450c17, 17beta-HSD and P-450arom, were measured at the developmental stages (days 2-9 of incubation) of chicken embryos by quantitative RT-PCR. Transcripts for all the genes studied, except for P-450arom were detected in all the developmental stages examined, indicating that mRNAs for the steroidogenic enzymes required to convert cholesterol to androgens are present in the avian embryo before gonadal differentiation. In contrast, P-450arom mRNA was detected in female embryos during days 5-9 of incubation but not in male embryos throughout incubation. The onset of P-450arom gene expression at day 5 coincides with the stage of gonadal differentiation, corroborating the role of estrogen in the process of gonadal differentiation in chicken.
Animals↗
Cardiac angiotensin-converting enzyme activity in myocardial infarction.
The cardiac renin-angiotensin system is regarded as an important modulator in the infarct heart. Little is known about their presence and regulation in human hearts. We measured angiotensin-converting enzyme (ACE) and renin activities at the aortic root and anterior interventricular vein (AIV) in 51 patients with previous myocardial infarction (MI): anterior wall MI in 31 and inferior wall MI in 20 and 33 control subjects. In the anterior wall MI group, the serum ACE activity was increased significantly in the AIV than in the aortic root (16.2 +/- 5.3 vs 15.3 +/- 5.0 nmol/min/ml, p <0.001), whereas the activity was not different between the aortic root and AIV in the control (14.4 +/- 3.7 vs 14.4 +/- 3.7 nmol/min/ ml) and in the inferior wall MI (16.5 +/- 4.8 vs. 17.0 +/-5.2 nmol/min/ml) groups. On the other hand, there was no significant difference in plasma renin activity between the AIV and aortic root in the 3 groups (control group, 1.0 +/- 0.5 vs 1.0 +/- 0.5 pg/ml/hour; anterior wall MI group, 1.3 +/- 0.8 vs 1.3 +/- 0.8 pg/ml/hour; inferior wall MI group, 1.2 +/- 0.7 vs 1.3 +/- 0.8 pg/ml/ hour). The difference in serum ACE activity between the AIV and aortic root had a significant positive linear correlation with pulmonary capillary wedge pressure (r = 0.606, p <0.001), and had a significant negative linear correlation with left ventricular ejection fraction (r = -0.620, p <0.001) in the anterior wall MI group. Serum ACE activity from the infarct region of the left ventricle was augmented in patients with MI, and the activity was increased in proportion to the severity of left ventricular dysfunction.
Adult↗
Circulating levels of secretory type II phospholipase A(2) predict coronary events in patients with coronary artery disease.
Background-The circulating levels of secretory nonpancreatic type II phospholipase A(2) (sPLA(2)) are increased in various chronic inflammatory diseases and the increase in the levels correlates with the disease severity. sPLA(2) may possibly play a role in atherogenesis and is highly expressed in atherosclerotic arterial walls that are known to have inflammatory features. Thus, this study prospectively examined whether circulating levels of sPLA(2) may have a significant risk and prognostic values in patients with coronary artery disease (CAD). Methods and Results-Plasma levels of sPLA(2) were measured in 142 patients with CAD and in 93 control subjects by a radioimmunoassay. The sPLA(2) levels had a significant and positive relations with serum levels of C-reactive protein, a marker of systemic inflammation, and with the number of the traditional coronary risk factors associated with individuals. Multivariate logistic regression analysis showed that higher levels of sPLA(2) (>246 ng/dL; 75th percentile of sPLA(2) distribution in controls) were a significant and independent risk factor for the presence of CAD. In multivariate Cox hazard analysis, the higher levels of sPLA(2) were a significant predictor of developing coronary events (ie, coronary revascularization, myocardial infarction, coronary death) during a 2-year follow-up period in patients with CAD independent of other risk factors, including CRP levels, an established inflammatory predictor. Conclusions-The increase in circulating levels of sPLA(2) is a significant risk factor for the presence of CAD and predicts clinical coronary events independent of other risk factors in patients with CAD; these results may reflect possible relation of sPLA(2) levels with inflammatory activity in atherosclerotic arteries.
Aged↗
Cloning and characterization of the gene for a new epithelial beta-defensin. Genomic structure, chromosomal localization, and evidence for its constitutive expression.
Mammalian beta-defensins are endogenous cysteine-rich peptide antibiotics that are produced either by epithelial cells lining the respiratory, digestive, and urogenital tracts or by granulocytes and macrophages. A growing body of evidence has implicated these peptides in host defense, particularly mucosal innate immunity. We previously reported the cloning of the full-length cDNA for a porcine beta-defensin (pBD-1), which was found to be expressed throughout the airway and oral mucosa. Here, we provide the structural organization of the pBD-1 gene, showing that the entire gene spans approximately 1.9 kilobases with two short exons separated by a 1.5-kilobase intron. Fluorescence in situ hybridization mapped the pBD-1 gene to porcine chromosome 15q14-q15. 1 within a region of conserved synteny to the chromosomal locations of human and mouse alpha- and beta-defensins. We also provide several independent lines of evidence showing that the pBD-1 gene is expressed constitutively during inflammation and infection, despite its resemblance to many inducible epithelial beta-defensins in amino acid sequence, genomic structure, and sites of expression. First, stimulation of primary porcine tongue epithelial cells with lipopolysaccharide, tumor necrosis factor-alpha, and interleukin (IL)-1beta failed to up-regulate the expression of pBD-1 mRNA. Second, pBD-1 gene expression was not enhanced in either digestive or respiratory mucosa of pigs following a 2-day infection with Salmonella typhimurium or Actinobacillus pleuropneumoniae. Last, direct transfection of the pBD-1 gene promoter into NIH/3T3 cells showed no difference in reporter gene activity in response to stimulation by lipopolysaccharide and IL-1beta. The constitutive expression of pBD-1 in airway and oral mucosa, which is consistent with a lack of consensus binding sites for nuclear factor-kappaB or NF-IL-6 in its promoter region, suggests that it may play a surveillance role in maintaining the steady state of microflora on mucosal surfaces.
3T3 Cells↗
Association of plasma levels of activated protein C with recanalization of the infarct-related coronary artery after thrombolytic therapy in acute myocardial infarction.
Protein C is one of the most important antithrombotic components. After activation by the thrombin-thrombomodulin complex on endothelial cells, activated protein C (APC) inactivates factors Va and VIIIa, which leads to the inhibition of thrombin formation. We examined the association of plasma levels of APC with the responsiveness to coronary thrombolytic therapy of the infarct-related coronary artery in patients with acute myocardial infarction (AMI). Plasma levels of APC, thrombin-antithrombin III complex (TAT), and plasminogen activator inhibitor (PAI) activity were measured in 32 consecutive AMI patients who underwent coronary angiography followed by thrombolytic therapy, and compared to the measurements in 23 control subjects. On admission, APC levels (ng/mL) were significantly elevated in patients with AMI, as compared with controls (2.5+/-0.4 vs. 1.2+/-0.2, 1.3+/-0.2, respectively, p<0.01). At discharge, plasma levels in AMI patients decline to values not significantly different from those in controls. (1.2+/-0.2, 1.3+/-0.2, respectively). TAT levels (ng/mL) were different among the groups in a fashion similar to that of APC (14.1+/-3.1 on admission vs. 3.3+/-0.4 at discharge, 1.8+/-0.1 in the control subjects, respectively, p<0.01). PAI activity levels (IU/mL) were higher on admission than at discharge and higher than the control subjects (19.7+/-1.8 vs. 10.5+/-1.0, 5.4 +/- 0.7, respectively, p<0.01). Thirty-two patients with AMI were classified into two groups according to the results of thrombolysis: the success group (24 patients) and the failure group (eight patients). APC levels were higher in the failure group than in the success group (5.1+/-0.7 vs. 1.6+/-0.2, p<0.01). TAT levels were also higher in the failure group than in the success group (30.8+/-9.6 vs. 8.6+/-1.7, p<0.01). PAI activity levels (IU/mL) were lower in the failure group than in the success group (13.5+/-3.1 vs. 21.7+/-2.1, p<0.05). There were correlations between APC and TAT levels both on admission (r=0.75, p<0.0001) and at discharge (r=0.71, p<0.0001). Elevated APC was thought to correlate with increased thrombin generation in patients with AMI. This study demonstrated that there was a significant relation between plasma APC level and the responsiveness to thrombolytic therapy of the infarct artery. This study may also indicate that increased thrombin generation is a cause of the resistance to thrombolytic therapy.
Acute Disease↗
Remnant lipoprotein levels in fasting serum predict coronary events in patients with coronary artery disease.
BACKGROUND: Remnant lipoproteins are atherogenic, but assays of remnants have not been available in routine clinical laboratories because of the lack of practical and validated methods. A simple and reliable method for such an assay, using an immunochemical approach, has recently been developed. This study prospectively examined whether remnant lipoprotein levels in fasting serum, measured by our method, may have prognostic value in patients with coronary artery disease (CAD). METHODS AND RESULTS: Remnant lipoprotein levels in fasting serum were measured in 135 patients with CAD by an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. Patients were followed up for </=36 months until occurrence of 1 of the following clinical coronary events: recurrent or refractory angina pectoris requiring coronary revascularization, nonfatal myocardial infarction, or cardiac death. Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with the highest tertile of remnant levels (>5.1 mg cholesterol/dL; 75th percentile of distribution of remnant levels) than in those with the lowest tertile of remnant levels (</=3.3 mg cholesterol/dL; 50th percentile of the distribution). Higher levels of remnants were a significant and independent predictor of developing coronary events in multivariate Cox hazard analysis including the following covariates: extent of coronary artery stenosis, age, sex, smoking, hypertension, diabetes mellitus, hypercholesterolemia, low HDL cholesterol, and hypertriglyceridemia. CONCLUSIONS: Higher levels of remnant lipoproteins in fasting serum predict future coronary events in patients with CAD independently of other risk factors. Thus, measurement of fasting remnant levels, assessed by the current immunoseparation method, may be helpful in assessment of CAD risk.
Adult↗
T-786-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm.
BACKGROUND: Coronary spasm plays an important role in the pathogenesis of ischemic heart diseases in general. However, the precise mechanism(s) responsible for coronary spasm remains to be elucidated, and we examined the molecular genetics of coronary spasm. METHODS AND RESULTS: We searched for the possible mutations in the endothelial nitric oxide synthase (eNOS) gene in patients with coronary spasm. In this study, we demonstrate the existence of 3 linked mutations in the 5'-flanking region of the eNOS gene (T-786-->C, A-922-->G, and T-1468-->A). The incidence of the mutations was significantly greater in patients with coronary spasm than in the control group (P<0.0001). Multiple logistic regression analysis with forward stepwise selection using the environmental risk factors and the eNOS gene variant revealed that the most predictive independent risk factor for coronary spasm was the mutant allele (P<0.0001). As assessed by luciferase reporter gene assays, the T-786-->C mutation resulted in a significant reduction in eNOS gene promoter activity (P<0.05), whereas neither the A-922-->G nor the T-1468-->A mutation had any affect. CONCLUSIONS: Taken together, these findings strongly suggest that the T-786-->C mutation in the eNOS gene reduces the endothelial NO synthesis and predisposes the patients with the mutation to coronary spasm.
Adult↗
Heightened tissue factor associated with tissue factor pathway inhibitor and prognosis in patients with unstable angina.
BACKGROUND: This study was designed to evaluate the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with unstable angina and investigate whether there is a relationship between these levels and unfavorable outcome. METHODS AND RESULTS: The plasma TF and free TFPI antigen levels were determined in plasma samples taken from 51 patients with unstable angina, 56 with stable exertional angina, and 55 with chest pain syndrome. The plasma TF and free TFPI antigen levels were higher in the unstable angina group than in the stable exertional angina and chest pain syndrome group. There was a good correlation between TF and TFPI. We established borderline as maximum level in the patients with chest pain syndrome. Seven patients (of the 22 in the high TF group) required revascularization to control their unstable angina during in-hospital stay. On the other hand, only 1 of the 29 patients in the low TF group required myocardial revascularization. Four patients of the 14 patients in the high free TFPI group required myocardial revascularization during in-hospital stay, and 4 of the 37 patients in the low free TFPI group required myocardial revascularization. We compared the TF and free TFPI levels between the cardiac event (+) group and cardiac event (-) group. TF levels were significantly higher in the cardiac event (+) group than in the cardiac event (-) group. CONCLUSIONS: We have demonstrated that not only the plasma TF levels but also the plasma-free TFPI levels are elevated in patients with unstable angina. Patients with unstable angina and heightened TF and free TFPI are at increased risk for unfavorable outcomes. The heightened TF level was a more important predictor in patients with unstable angina.
Adult↗
Significance of late diastolic potential preceding Purkinje potential in verapamil-sensitive idiopathic left ventricular tachycardia.
BACKGROUND: Verapamil-sensitive idiopathic left ventricular tachycardia (VT) is due to reentry with an excitable gap. A late diastolic potential (LDP) is recorded during endocardial mapping of this VT, but its relation to the reentry circuit and significance in radiofrequency (RF) ablation remain to be elucidated. METHODS AND RESULTS: Sixteen consecutive patients with this specific VT were studied (12 men and 4 women; mean age, 32 years). In all patients, sustained VT was induced and during left ventricular endocardial mapping, LDP preceding Purkinje potential (PP) was recorded at the basal (11 patients), middle (3 patients), or apical septum (2 patients). The area with LDP recording was confined to a small region (0.5 to 1.0 cm2) in each patient and was included in the area where PP was recorded (2 to 3 cm2). The relative activation times of LDP, PP, and local ventricular potential (V) at the LDP recording site to the onset of QRS complex were -50.4+/-18.9, -15.2+/-9.6, and 3.0+/-13.3 ms, respectively. The earliest ventricular activation site during VT was identified at the posteroapical septum and was more apical in the septum than the region with LDP in every patient. In 9 patients, VT entrainment was done by pacing from the right ventricular outflow tract while recording LDP. During entrainment, LDP was orthodromically captured, and as the pacing rate was increased, the LDP-to-PP interval was prolonged, whereas stimulus-to-LDP and PP-to-V interval were constant. In 3 patients, the pressure applied to the catheter tip at the LDP region resulted in conduction block between LDP and PP and in VT termination. RF energy application at the LDP recording site successfully eliminated VT. CONCLUSIONS: LDP was suggested to represent the excitation at the entrance to the specialized area with a conduction delay in response to the increase in the rate within the critical slow conduction zone participating in the reentry circuit of this VT. LDP can be a useful marker for successful RF ablation for this VT.
Action Potentials↗
Effects of aspirin and trapidil on cardiovascular events after acute myocardial infarction. Japanese Antiplatelets Myocardial Infarction Study (JAMIS) Investigators.
Aspirin therapy confers conclusive net benefits in the acute phase of evolving myocardial infarction, but no clear evidence of benefit from the long-term use of aspirin after acute myocardial infarction (AMI) has been shown in any single study. This multicenter study, the Japanese Antiplatelets Myocardial Infarction Study, was performed to find out whether aspirin or trapidil would improve clinical outcome compared with no antiplatelets in postinfarction patients. The study was a multicenter, open-label, randomized controlled trial of aspirin 81 mg/day, trapidil 300 mg/day, and no antiplatelets in patients with AMI admitted within 1 month from the onset of symptoms. Seven hundred twenty-three patients were enrolled at 70 hospitals in 18 prefectures of Japan; 250 were randomly assigned to treatment with 81 mg aspirin (aspirin group), 243 to that with trapidil (trapidil group), and 230 were not given antiplatelet agents. The mean follow-up period was 475 days. This study demonstrated that long-term use of aspirin at the dose of 81 mg/day reduced the incidence of recurrent AMI compared with the group receiving no antiplatelets after AMI (p = 0.0045) and that trapidil also reduced the occurrence of reinfarction compared with the group receiving no antiplatelets, but the difference was not significant (p = 0.0810). The incidence of cardiovascular events including cardiovascular death, reinfarction, uncontrolled unstable angina requiring admission to hospital, and nonfatal ischemic stroke was reduced in the group receiving 300 mg trapidil daily compared with the group receiving no antiplatelets (p = 0.0039). The use of aspirin 81 mg/day provided almost no benefit over no antiplatelets therapy in the incidence of cardiovascular events. In conclusion, low-dose aspirin (81 mg) effectively prevented recurrent AMI in postinfarction patients after thrombolysis or coronary angioplasty when used over a long term. Furthermore, the long-term use of trapidil resulted in a significant reduction in the incidence of cardiovascular events.
Aged↗
Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis.
CREB-binding protein (CBP) and the closely related adenovirus E1A-associated 300-kD protein (p300) function as coactivators of transcription factors such as CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. To study the roles of CBP in embryonic development, we generated CBP homozygous mutant mouse embryos that expressed a truncated form of CBP protein (1-1084 out of 2441 residues). The embryos died between embryonic days 9.5 (E9.5) and E10.5 and exhibited a defect in neural tube closure. They appeared pale and showed decreases in erythroid cells and colony-forming cells (CFCs) in the yolk sac, suggesting defects in primitive hematopoiesis. Immunohistochemistry with an anti-PECAM antibody showed a lack of vascular network formation. Organ culture of para-aortic splanchnopleural mesoderm (P-Sp) with stromal cells (OP9) showed an autonomous abnormality of putative endothelial precursors, which may induce the microenvironmental defect in hematopoiesis. In addition, these defects were partially rescued by the addition of VEGF to this culture. Our analyses demonstrate that CBP plays an essential role in hematopoiesis and vasculo-angiogenesis.
Animals↗
Outcome of target sites escaping high-grade (>70%) restenosis after percutaneous transluminal coronary angioplasty.
This study examined the fate of target sites that escaped high-grade restenosis (> or = 70% diameter narrowing) after percutaneous transluminal coronary angioplasty. Although favorable long-term prognosis after successful percutaneous transluminal coronary angioplasty is well documented, little is known about the stability of target sites. Long-term follow-up (mean 6.5 years, range 1.0 to 12.0) was performed in 693 patients with 948 narrowings (stenosis <70% in diameter at follow-up coronary angiography). Among them, 249 patients (36%) with 303 target sites received late follow-up coronary angiography. The relation of target sites to the culprit lesions for coronary events or newly developed angina was angiographically reviewed and progression/regression was also examined, focusing on the target sites. Regression was observed in 16 of 255 target sites in subjects with <50% stenosis and in 21 of 48 sites in the group with midgrade stenosis of 50% to 69% luminal narrowing (16 of 255, 6.3% vs 21 of 48, 43.8%, p <0.001). Progression was observed in 33 and 4 sites (33 of 255, 12.9% vs 4 of 48, 8.3%; p = NS) in each group, respectively. The rest remained within the same range of stenosis. Culprit lesions for 2 acute myocardial infarctions, 7 unstable anginas, and 17 newly developed anginas were related to the original target sites. Three lesions developed in the midgrade stenosis group. Those 26 lesions were a component of 8.6% of 303 angiographically confirmed sites and 2.7% of total target sites. Target sites that escape high-grade restenosis frequently regress and become stable plaques and rarely trigger coronary events.
Aged↗
Suppression of atherosclerotic development in Watanabe heritable hyperlipidemic rabbits treated with an oral antiallergic drug, tranilast.
BACKGROUND: Inflammatory and immunological responses of vascular cells have been shown to play a significant role in the progression of atheromatous formation. Tranilast [N-(3,4-dimethoxycinnamoyl) anthranillic acid] inhibits release of cytokines and chemical mediators from various cells, including macrophages, leading to suppression of inflammatory and immunological responses. This study tested whether tranilast may suppress atheromatous formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. METHODS AND RESULTS: WHHL rabbits (2 months old) were given either 300 mg x kg-1 x d-1 of tranilast (Tranilast, n=12) or vehicle (Control, n=13) PO for 6 months. Tranilast treatment was found to suppress the aortic area covered with plaque. Immunohistochemical analysis showed that there was no difference in the percentage of the RAM11-positive macrophage area and the frequency of CD5-positive cells (T cells) in intimal plaques between Tranilast and Control. Major histocompatibility complex (MHC) class II expression in macrophages and interleukin-2 (IL-2) receptor expression in T cells, as markers of the immunological activation in these cells, was suppressed in atheromatous plaque by tranilast treatment. Flow cytometry analysis of isolated human and rabbit peripheral blood mononuclear cells showed that an increase in expression both of MHC class II antigen on monocytes by incubation with interferon-gamma and of IL-2 receptor on T cells by IL-2 was suppressed by the combined incubation with tranilast. CONCLUSIONS: The results indicate that tranilast suppresses atherosclerotic development partly through direct inhibition of immunological activation of monocytes/macrophages and T cells in the atheromatous plaque.
Administration, Oral↗
Plasma soluble intercellular adhesion molecule-1 levels in coronary circulation in patients with unstable angina.
It has been suggested that active inflammation plays an important role in the pathogenesis of acute coronary syndromes, including unstable angina. Intracellular adhesion molecule-1 (ICAM-1) is a major ligand on the endothelial cells for adherence of the activated polymorphonuclear leukocytes. Recently, it has been demonstrated that the soluble form of ICAM-1 has been detected in human serum and has been increased in many other inflammatory or autoimmune disorders. To evaluate the involvement of ICAM-1 in unstable angina, we examined plasma soluble ICAM-1 (sICAM-1) levels in coronary circulation. The plasma sICAM-1 levels in the coronary sinus and aortic root were simultaneously examined in 20 patients with unstable angina, 19 patients with stable exertional angina, and 16 control subjects. The plasma levels of sICAM-1 were measured by enzyme-linked immunosorbent assay. The mean plasma sICAM-1 levels (nanograms per milliliter) both in the coronary sinus and aortic root were significantly higher (p <0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (217+/-14 vs 126+/-8; 120+/-10 in the coronary sinus, 202+/-13 vs 125+/-9; 123+/-10 in the aortic root). Furthermore, the mean value was higher in the coronary sinus than in the aortic root in patients with unstable angina. There were no significant differences in the values between in the coronary sinus and aortic root in patients with stable exertional angina and control subjects. Thus, sICAM-1 release is increased, especially in coronary circulation in unstable angina.
Aged↗
Plasma tissue factor pathway inhibitor and tissue factor antigen levels after administration of heparin in patients with angina pectoris.
The hypercoagulability is associated with expression of tissue factor in patients with angina. Tissue factor pathway inhibitor regulates the extrinsic coagulation pathway mediated by tissue factor. Plasma samples were obtained from 14 patients with angina pectoris and 9 with chest pain syndrome before and 5, 30, 60, and 120 minutes after administration of heparin (50 IU/kg). The tissue factor and prothrombin fragment 1+2 levels before administration were elevated in patients with angina pectoris and were reduced to the levels of chest pain syndrome after the administration. The free tissue factor pathway inhibitor levels after the administration were higher in patients with angina pectoris than in patients with chest pain syndrome. Plasma tissue factor pathway inhibitor levels correlated positively with plasma tissue factor and prothrombin fragment 1+2 levels. We showed that plasma-free TFPI levels after administration of heparin, which may indicate endothelial cell associated TFPI levels, increased in patients with angina pectoris compared with patients with chest pain syndrome. Increased endothelial cell associated TFPI was associated with hypercoagulability in patients with angina pectoris. These may help to explain the reduction in thrombotic risk associated with the use of heparin.
Angina Pectoris↗
Co-localization of tissue factor and tissue factor pathway inhibitor in coronary atherosclerosis.
Tissue factor (TF) initiates the extrinsic pathway of blood coagulation by acting as a cofactor for Factor VII. Inhibition of the Factor VIIa-TF complex is mediated by the tissue factor pathway inhibitor (TFPI), which is a serine protease inhibitor with three Kunitz-type domains. The localization of TF and TFPI protein has been examined immunohistochemically in various atherosclerotic lesions of coronary arteries from 22 autopsy cases and their messenger RNA expression has been confirmed by reverse transcription-polymerase chain reaction. Four types of atherosclerotic lesion (types I, II, III, and IV) were classified according to the method described by Stary et al. TF and TFPI were localized in endothelial cells, macrophages, macrophage-derived foam cells, and smooth muscle cells in the intimal lesions, medial smooth muscle cells, and endothelial cells of the microvessels in the adventitia. Immunohistochemical double staining revealed the co-localization of TF and TFPI in the endothelial cells and macrophages in four types of atherosclerotic lesions. In type III and IV lesions, the number of TF- and TFPI-positive cells was increased, accompanied by extracellular localization of TF and TFPI in the lipid core of atherosclerotic plaques. Fibrin deposition was found around TF- and TFPI-positive macrophages and in the lipid core of atherosclerotic plaques. TF and TFPI messenger RNA were detected more frequently in coronary arteries with type III and IV lesions than in those with type I and II lesions. The co-localization of TF and TFPI was demonstrated in various atherosclerotic lesions of coronary arteries and was shown to be intimately related to fibrin deposition in advanced atherosclerotic plaques. The co-localization of TF and TFPI may thus be closely associated with thrombogenicity in atherosclerotic lesions of coronary arteries.
Aged↗