Biomedical subjects

Michihiro Yoshimura

Publications and source records attributed to Michihiro Yoshimura.

72 records · Page 4Linked to original sources

PubMed2003

Association of polymorphism in glutamate-cysteine ligase catalytic subunit gene with coronary vasomotor dysfunction and myocardial infarction.

OBJECTIVES: The purpose of this study was to test the hypothesis that polymorphisms in the promoter region of the glutamate-cysteine ligase catalytic subunit (GCLC) gene may be associated with coronary endothelial vasomotor dysfunction and myocardial infarction (MI). BACKGROUND: Glutamate-cysteine ligase is a rate-limiting enzyme for synthesis of glutathione (GSH) that plays a crucial role in the intracellular antioxidant defense systems. Oxidants transcriptionally upregulate the GCLC gene for GSH synthesis, providing a protective mechanism against oxidant-induced endothelial dysfunction or activation, which plays a pathogenetic role in cardiovascular diseases. METHODS: The association of the possible polymorphisms with coronary arterial diameter responses to acetylcholine was determined in 62 male subjects. The frequency of polymorphisms was compared between 255 male patients with MI and 179 male control subjects. RESULTS: We found a polymorphism (-129C/T) in which the T allele showed lower promoter activity (50% to 60% of the activity of the C allele) in response to H(2)O(2) in human endothelial cells. Endothelium-dependent dilation of coronary arteries was impaired in subjects with the -129T allele (n = 31), as compared with the age-matched subjects without the -129T allele (n = 31). The T allele was highly frequent in patients with MI as compared with control subjects, and it was a significant risk factor for MI, independent of traditional coronary risk factors (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.08 to 3.03; p = 0.03). CONCLUSIONS: The -129T polymorphism of the GCLC gene may suppress the GCLC gene induction response to an oxidant, and it is implicated in coronary endothelial vasomotor dysfunction and MI.

Adult↗

PubMed2003

Inhibitory effect of natriuretic peptides on aldosterone synthase gene expression in cultured neonatal rat cardiocytes.

BACKGROUND: Although previously thought to be synthesized solely in adrenal cortex, we have recently showed that aldosterone is also produced in and the expression of CYP11B2 mRNA was induced in the failing or hypertensive human ventricle. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones with wide biological effects, including inhibition of renin and aldosterone production. We hypothesized that natriuretic peptides reduce the expression of CYP11B2 mRNA in the heart. METHODS AND RESULTS: To test this hypothesis, we examined whether endogenous or exogenous natriuretic peptides reduce the expression of CYP11B2 mRNA using real-time reverse transcription-polymerase chain reaction. By using HS 142-1, a functional guanylyl cyclase-A type receptor antagonist, we showed that angiotensin II (AngII) pretreated with HS 142-1 increased CYP11B2 mRNA expression (1.62+/-0.12-fold, HS 142-1+AngII 10(-7) mol/L versus AngII 10(-7) mol/L alone, P<0.0001). The treatment with exogenous (10(-6) mol/L) ANP and BNP reduced CYP11B2 mRNA expression (ANP, P=0.0042; BNP, P=0.0012). CONCLUSIONS: We showed that endogenous and exogenous natriuretic peptides reduced CYP11B2 mRNA expression in cultured neonatal rat cardiocytes. This may inhibit the cardiac renin-angiotensin-aldosterone system by suppressing the gene expression of CYP11B2 and restraining cardiac hypertrophy and fibrosis.

Angiotensin II↗

PubMed2003

Increased plasma thioredoxin in patients with acute myocardial infarction.

BACKGROUND AND HYPOTHESIS: Thioredoxin is an important biomarker for oxidative stress. We investigated whether thioredoxin levels were elevated in patients with acute myocardial infarction (AMI) and were associated with the results of coronary reperfusion. METHODS: The present study determined plasma thioredoxin levels in 51 patients with AMI, 30 patients with stable exertional angina (SEA), and 30 patients with chest pain syndrome (CPS). Plasma sampling was performed on admission, at 12 h, 1 week, 2 weeks, and 4 weeks in patients with AMI, and after admission in patients with SEA and CPS. RESULTS: Plasma thioredoxin levels on admission were higher in patients with AMI than in those with SEA and CPS. Plasma thioredoxin levels in patients with AMI were decreased in 12 h without further change thereafter. However, thioredoxin levels in patients with AMI remained higher than in those with SEA. In multivariate analysis, higher levels of thioredoxin on admission were a risk factor for failure in emergent reperfusion therapy in patients with AMI independent of other factors. CONCLUSION: Plasma thioredoxin levels are elevated in patients with AMI, and higher thioredoxin levels may predict subsequent failed coronary reperfusion therapy in patients with AMI.

Adult↗

PubMed2003

Plasminogen activator inhibitor contributes to the coronary wall thickening in patients with angiographically normal coronary.

INTRODUCTION: Angiographically normal coronary arteries have concealed intimal thickening that importantly contribute to coronary arterial disease activity. Increased plasma levels of plasminogen activator inhibitor (PAI) are associated with myocardial infarction and atherosclerosis. However, it remains unclear whether the PAI contributes to vascular wall thickening detected by intravascular ultrasound (IVUS) in normal coronary angiogram. The aim of this study was to evaluate if the PAI activity contributes to the extent of atherosclerotic changes in angiographically normal coronary arteries using IVUS technique. MATERIALS AND METHODS: We studied 33 consecutive patients with normal coronary angiograms. These patients were divided into a high level of plasma PAI activity group (H-PAI; n=12) and a normal range of PAI activity group (N-PAI; n=21), according to the plasma PAI activity levels. RESULTS: The average of "percent intima+media area (%I+M area)" and "maximal intima+media (I+M) thickness" were significantly greater in the H-PAI group as compared with those in the N-PAI group (p<0.05). Minimal lumen diameter and lumen area were comparable between these groups. The plasma PAI activity level was the independent predictor of increase in maximal I+M thickness, in multiple regression analysis with the traditional risk factors as covariates. CONCLUSIONS: Thickened intima+media of angiographically normal coronary arteries were associated with high plasma level of PAI activity, independently of other traditional risk factors. PAI may contribute to the pathogenesis of coronary intimal thickening that might increase coronary arterial tone.

Cell Division↗

PubMed2003

Plasma thioredoxin levels and platelet aggregability in patients with acute myocardial infarction.

BACKGROUND: Oxidative stress is thought to play an important role in atherosclerotic vascular disease. Recently, it has become possible to quantitatively measure thioredoxin, a marker of oxidative stress in human plasma. A platelet aggregometer that uses laser-light scattering enables minimal changes in platelet aggregability to be monitored; however, the relationship between oxidative stress and platelet aggregability in vivo is not well understood. METHODS: We investigated plasma thioredoxin levels and platelet aggregability, in particular small platelet aggregates, in 45 patients with acute myocardial infarction (AMI); we compared the results with 33 patients with stable exertional angina (SEA) and 30 patients with chest pain syndrome (CPS). RESULTS: The plasma thioredoxin levels and the degree of small platelet aggregates were higher in the AMI group than in the SEA and the CPS groups: in the AMI group, at 4 weeks after admission, both of those parameters were significantly decreased (P <.01), but they were still higher (P <.05) than in the SEA or the CPS group. There was a significant positive correlation between small platelet aggregates and plasma thioredoxin levels (rho = 0.354, P =.0002). We divided the AMI patients into 2 groups according to the 75 percentile of plasma thioredoxin levels on admission. At the chronic phase, the left ventricular ejection fraction was significantly higher in the lower thioredoxin group than in the higher thioredoxin group. CONCLUSIONS: We showed that plasma thioredoxin levels and platelet aggregability increased concomitantly in patients with AMI. In these patients, increased plasma thioredoxin was associated with platelet hyperaggregability and lower left ventricular ejection fraction.

Adult↗

PubMed2003

Synergistic interaction of T-786-->C polymorphism in the endothelial nitric oxide synthase gene and smoking for an enhanced risk for coronary spasm.

OBJECTIVE: We previously reported that a T-786-->C polymorphism in the 5'-flanking region of the endothelial nitric oxide synthase gene and smoking were independently associated with coronary spasm; however, the interaction between this polymorphism and smoking remains to be elucidated. METHODS: We analyzed 209 men and 238 women who were admitted consecutively at our institution; all subjects received an intracoronary injection of acetylcholine (ACh) while undergoing coronary angiography for evaluation of chest pain: all subjects had no significant coronary stenosis. We divided these subjects into four groups: non-smokers with T/T genotype (Control Group A); non-smokers with C/T or C/C genotype (Group B); smokers with T/T genotype (Group C); and smokers with C/T or C/C genotype (Group D). We further examined quantitative coronary angiographies of the left anterior descending coronary artery in a subset of 54 consecutive men and 53 consecutive women. RESULTS: The frequencies of coronary spasm in Group B (male: 61%, female: 78%), Group C (62%, 59%) and Group D (91%, 92%) were significantly higher than in Group A (30%, 38%). In the males, ACh-induced vasoconstriction was greatest in Group D, and the change was weakest in Group A. In the females, ACh-induced vasoconstrictions were significantly greater in Groups B, C and D than in Group A. The T-786-->C polymorphism and smoking combine to increase the risk of coronary spasm.

Acetylcholine↗

PubMed2003

Platypnea - orthodeoxia syndrome with atrial septal defect.

A 75-year old man was referred to hospital for symptomatic hypoxemia. He did not complain of dyspnea while supine, but while sitting or standing, he experienced dyspnea with severe hypoxemia. He did not have any pulmonary diseases that could cause dyspnea. Transesophageal echocardiography revealed an atrial septal aneurysm with a small atrial septal defect (ASD) and a mild left-to-right shunt through the ASD when the patient was supine. However, when he became upright, a severe right-to-left shunt occurred and the arterial oxygen saturation decreased from 96% to 80% with dyspnea. Cardiac catheterization revealed normal pulmonary artery pressure. He was therefore diagnosed as having platypnea - orthodeoxia syndrome. Magnetic resonance imaging of the chest showed a deformity of the atrium associated with elongation of the ascending aorta. The ASD was closed surgically and the dyspnea and hypoxemia that occurred while he was upright completely resolved.

Aged↗

PubMed2003

Increased serum matrix metalloproteinase-1 concentration predicts advanced left ventricular remodeling in patients with acute myocardial infarction.

The left ventricular ejection fraction (LVEF) is one of the major prognostic factors after acute myocardial infarction (AMI) and matrix metalloproteinase-1 (MMP-1) is an enzyme responsible for extracellular collagen degradation and remodeling. The present study investigated whether the concentration of serum MMP-1 was associated with the LVEF after AMI. Blood was sampled on admission, and at 24 h, 3 days, 7 days, 2 weeks and 4 weeks in 24 patients with their first AMI. Left ventriculography was performed 4 weeks after the onset of AMI and the LVEF was calculated by center line method. MMP-1 concentrations were higher at 7 days and at 2 weeks than on admission (p<0.001), and at 7 days (r=-0.655, p=0.0005) and at 2 weeks (r=-0.636, p=0.0008) were negatively correlated with the LVEF. The patients with AMI were divided into high and low LVEF groups according to the results of left ventriculography. Although there were no differences in the clinical characteristics between the 2 LVEF groups, the MMP-1 concentrations at 24 h (p<0.01), 7 days (p<0.01) and 2 weeks (p<0.05) were lower in the high LVEF group than in low LVEF group. A high concentration of MMP-1 at the subacute phase after AMI predicts advanced left ventricular remodeling.

Aged↗

PubMed2003

Formation of platelet microaggregates correlates with adverse clinical outcome in patients with coronary artery disease.

Platelet activation plays a pivotal role in the pathogenesis of acute coronary syndromes. Laser-light scattering in a platelet aggregometer was used to evaluate aggregate size and number quantitatively. Small platelet aggregates ultimately develop into medium and then large platelet aggregates. Thus the measurement of small platelet aggregates is important in the evaluation of thrombus formation. We examined the relationship between small platelet aggregates and the occurrence of subsequent cardiovascular events. We followed-up 204 patients (149 men and 55 women, mean age 68 +/- 9 years) with coronary artery disease (CAD) for 48 months. Blood sampling to determine platelet aggregation was performed on the day of hospital discharge. The degree of small platelet aggregates [relative risk 4.34, 95% confidence interval (1.62-11.7), p = 0.004] and low left-ventricular ejection fraction [relative risk 2.88, 95% confidence interval (1.23-6.73), p = 0.015] were independent predictors of the occurrence of cardiovascular events in multivariate Cox hazard analysis. In Kaplan-Meier analysis, the degree of small platelet aggregates correlated with the probability of cardiovascular event occurrence. In patients with CAD, an increase in small platelet aggregates is closely correlated with the future occurrence of cardiovascular events

Adult↗

PubMed2002

Comparison of urinary biopyrrin levels in acute myocardial infarction (after reperfusion therapy) versus stable angina pectoris and their usefulness in predicting subsequent cardiac events.

We examined the relation between oxidative stress and cardiac events in patients with acute myocardial infarction (AMI). There is now increasing evidence that reactive oxygen species cause reperfusion injury to the previously ischemic myocardium after reperfusion. We measured urinary biopyrrin/creatinine levels, an oxidative stress marker, in 41 patients with AMI, 34 patients with stable angina pectoris (SAP), and 29 control subjects. In the patients with AMI, urine samples were taken before, at 4 and 24 hours, and at 1 and 2 weeks after reperfusion therapy. Of these 41 patients with AMI, 38 received reperfusion therapy, and the urinary biopyrrin/creatinine levels (micromol/g.creatinine) before reperfusion were significantly higher than those of the other 2 groups (AMI 4.24 +/- 0.49, SAP 2.45 +/- 0.15, control subjects 2.31 +/- 0.16; p = 0.0003 vs AMI). The onset of reperfusion significantly increased the levels of urinary biopyrrins/creatinine, and this time course was mapped out, peaking at 4 hours (8.21 +/- 0.96 vs 4.24 +/- 0.49 before, p = 0.0001), and decreasing to control levels between 24 hours and 7 days. The peak levels of urinary biopyrrins/creatinine were higher in the positive cardiac event group than in the negative cardiac event group (11.89 +/- 1.77 vs 7.57 +/- 1.00 micromol/g.creatinine, p = 0.029). These findings add further evidence that oxidative stress contributes to the complications of reperfusion injury, and suggest that urinary assessment of biopyrrins may be useful in predicting subsequent cardiac events after reperfusion in AMI.

Aged↗

PubMed2002

Polymorphism in the 5'-flanking region of human glutamate-cysteine ligase modifier subunit gene is associated with myocardial infarction.

BACKGROUND: Human glutamate-cysteine ligase (GCL) is a rate-limiting enzyme for the synthesis of glutathione that plays a crucial role in antioxidant defense mechanisms in most mammalian cells, including vascular cells. Oxidants transcriptionally upregulate GCL genes for glutathione synthesis, providing a protective mechanism against oxidative stress-induced cellular dysfunction. This study examined the hypothesis that variation in the GCL genes may be associated with coronary artery disease in which oxidative stress plays a pathogenetic role. METHODS AND RESULTS: We searched for the common variants in the 5'-flanking region of the GCL modifier subunit (GCLM) gene in patients with myocardial infarction (MI). We found a polymorphism (-588C/T) in which the T allele showed lower promoter activity (40% to 50% of C allele) in response to oxidants in the luciferase reporter gene assay. Allele frequencies were determined by polymerase chain reaction-based analysis of restriction fragment length polymorphism in 429 patients with MI and 428 control subjects (as defined by angiography) in Kumamoto Prefecture, Japan. The frequency of the T polymorphism was significantly higher in the MI group than in the control group (CT and TT genotypes: 31.5% in MI group versus 19.2% in control group; P<0.001). In multiple logistic regression analysis, the T polymorphism was a risk factor for MI independent of traditional coronary artery disease risk factors (odds ratio, 1.98; 95% confidence interval, 1.38 to 2.83; P<0.001). CONCLUSIONS: These findings suggest that the -588T polymorphism of the GCLM gene may suppress GCLM gene induction in response to oxidants and that it is a genetic risk factor for MI.

5' Flanking Region↗

PubMed2002

B-type natriuretic peptide as a marker of the effects of enalapril in patients with heart failure.

BACKGROUND: A-Type and B-type natriuretic peptides are cardiac hormones whose circulating levels reflect the severity of heart failure. It is not known how plasma levels of these hormones respond to changes in cardiac function that occur as a result of treatment with angiotensin-converting enzyme (ACE) inhibitors. METHODS: Enalapril was administered at 5 mg/d for 3 months in 24 patients with chronic heart failure, and for the next 3 months at 15 mg/d in the high-dose group (n = 12) and 5 mg/d in the low-dose group (n = 12). We measured plasma levels of A-type or B-type natriuretic peptides, as well as conventional measures of cardiac function, such as the cardiothoracic ratio, left ventricular end-diastolic volume, and percent fractional shortening. RESULTS: Mean (+/- SD) plasma levels of both hormones decreased promptly after 2 weeks of therapy (A-type natriuretic peptide: 140 +/- 107 pg/mL to 81 +/- 68 pg/mL, P = 0.01; B-type natriuretic peptide: 305 +/- 278 pg/mL to 190 +/- 178 pg/mL, P = 0.01). These reductions were sustained throughout therapy. In contrast, the cardiothoracic ratio, left ventricular end-diastolic dimension, and percent fractional shortening had not changed significantly after 3 months of treatment, although improvements were seen after 6 months of treatment. After 6 months, plasma levels of both A-type and B-type natriuretic peptides were significantly lower in the high-dose group than in the low-dose group (A-type natriuretic peptide: 48 +/- 25 pg/mL vs. 57 +/- 27 pg/mL, P = 0.01; B-type natriuretic peptide: 78 +/- 58 pg/mL vs. 139 +/- 61 pg/mL, P = 0.005), whereas no significant differences were observed in the other measures of cardiac function. CONCLUSION: Plasma levels of A-type and B-type natriuretic peptides appear to be more sensitive markers of heart failure than conventional echocardiographic parameters and cardiothoracic ratios. Measurement of these hormones might be useful for monitoring the effects of treatment with ACE inhibitors.

Aged↗

PubMed2002

Effects of perindopril on aldosterone production in the failing human heart.

The present study was designed to examine whether the production of aldosterone from the heart is suppressed by angiotensin-converting enzyme (ACE) inhibition in patients with heart failure. Forty-one patients with left ventricular systolic dysfunction were randomly divided into either the perindopril group (n = 21, perindopril 4 mg/day) or the placebo group (n = 20). Plasma levels of aldosterone and ACE activity were measured in the anterior interventricular vein, coronary sinus, and aortic root during cardiac catheterization. The levels of aldosterone as well as ACE activity were significantly higher at the anterior interventricular vein and the coronary sinus than at the aortic root in the placebo group (aldosterone: 92.1 +/- 9.0 vs 70.6 +/- 8.3 pg/ml [p <0.001]; 90.3 +/- 9.2 vs 70.6 +/- 8.3 pg/ml [p <0.001], respectively; ACE activity: 13.6 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], 13.4 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], respectively). On the other hand, there were no differences in the levels of aldosterone or ACE activity between the anterior interventricular vein and aortic root or between the coronary sinus and aortic root (aldosterone: 68.1 +/- 8.4 vs 69.9 +/- 9.4 pg/ml [p = NS]; 67.3 +/- 8.9 vs 69.9 +/- 9.4 pg/ml [p = NS], respectively; ACE activity: 9.7 +/- 0.8 vs 9.9 +/- 0.8 IU/L [p = NS]; 9.8 +/- 0.8 vs 9.9 +/- 0.8 IU/L, respectively) in the perindopril group. The levels of aldosterone as well as ACE activity were significantly lower at the anterior interventricular vein and coronary sinus in the perindopril group than in the placebo group. The difference in the level of aldosterone between the anterior interventricular vein and aortic root (Delta aldosterone [anterior interventricular vein - aortic root]) had a significant positive correlation with that of ACE activity (Delta ACE [anterior interventricular vein - aortic root]) (r = 0.536, p <0.001), whereas ACE activity in the aortic root had no significant correlation with either the aldosterone levels in the aortic root or Delta aldosterone (anterior interventricular vein - aortic root). Perindopril suppressed cardiac aldosterone production by mainly suppressing cardiac ACE activity in patients with heart failure. Thus, aldosterone production is activated in the failing ventricle and is suppressed by perindopril mainly via the suppression of cardiac ACE activity in patients with heart failure.

Aldosterone↗

PubMed2002

B-type natriuretic peptide after percutaneous transluminal septal myocardial ablation.

BACKGROUND: Plasma level of B-type natriuretic peptide is a sensitive marker of left ventricular dysfunction and the level is markedly elevated in patients with hypertrophic obstructive cardiomyopathy. Percutaneous transluminal septal myocardial ablation, a catheter-based treatment of hypertrophic obstructive cardiomyopathy, has been widely used as a new therapeutic option for the disease. This study was designed to evaluate clinical implications of natriuretic peptides after the new treatment. METHODS: Seven consecutive patients with hypertrophic obstructive cardiomyopathy unresponsive to usual medical treatments (age: 57.9+/-22.0 years) were enrolled in the study. Serial changes in atrial and B-type natriuretic peptide in plasma were examined after percutaneous transluminal septal myocardial ablation. RESULTS: Atrial and B-type natriuretic peptides levels (pg/ml, mean+/-S.D.) at baseline were higher in hypertrophic obstructive cardiomyopathy than in control (80.0+/-43.0 vs. 12.8+/-5.2, P<0.0001; 858.0+/-458.4 vs. 12.4+/-7.0, P<0.0001; respectively). Left ventricular outflow-tract pressure gradient (mmHg) immediately decreased from 115.3+/-23.3 to 30.6+/-12.4 (P<0.0001) after the treatment and concomitantly B-type natriuretic peptide level decreased (858.0+/-458.4 to 264.1+/-137.7, P=0.0084). The level re-increased and peaked at the 2nd day (634.4+/-429.6) and gradually decreased again until 4 weeks. Reduction rate of left ventricular outflow-tract pressure gradient between before and 4 weeks after percutaneous transluminal septal myocardial ablation positively correlated with that of B-type natriuretic peptide (r(2)=0.817, P=0.0053). Changes in atrial natriuretic peptide were not significant in contrast to those of B-type natriuretic peptide. CONCLUSIONS: Plasma B-type natriuretic peptide level could be useful to predict the effects of percutaneous transluminal septal myocardial ablation in patients with hypertrophic obstructive cardiomyopathy.

Adolescent↗

PubMed2002

Aldosterone is produced from ventricles in patients with essential hypertension.

This study was designed to examine whether aldosterone is produced from the hearts of patients with essential hypertension without left ventricular systolic dysfunction (LVSD). The study population consisted of 20 patients with essential hypertension without LVSD and 22 control subjects. Plasma levels of aldosterone, serum ACE activity, and B-type natriuretic peptide levels were measured in the anterior interventricular vein (AIV), coronary sinus, and aortic root during cardiac catheterization. The plasma aldosterone levels were significantly higher in AIV and coronary sinus than in aortic root (99+/-11 versus 88+/-10 pg/mL, P<0.01, and 100+/-12 versus 88+/-10 pg/mL, P<0.01, respectively) in the hypertension group. On the other hand, there were no significant differences in aldosterone levels for these sites in the control group. There were no significant differences in ACE activity levels between aortic root, AIV, and coronary sinus in either the hypertension or control group. The levels of B-type natriuretic peptide were significantly higher in AIV than in aortic root in both groups. The difference in aldosterone levels between AIV and aortic root (Delta Aldo[AIV-Ao]) had a significant positive correlation with the difference in ACE activity between AIV and aortic root (DeltaACE[AIV-Ao]) (r=0.501, P<0.05) in the hypertension group. Both Delta Aldo[AIV-Ao] and DeltaACE[AIV-Ao] had a significant positive correlation with diastolic blood pressure (r=0.498, P<0.05; r=0.577, P<0.01, respectively) in the hypertension group. We conclude that production of aldosterone is activated in the left ventricles in patients with essential hypertension without LVSD in proportion to the severity of hypertension.

Aldosterone↗

PubMed2002

Expression of aldosterone synthase gene in failing human heart: quantitative analysis using modified real-time polymerase chain reaction.

We have shown that aldosterone, previously thought to be synthesized solely in the adrenal cortex, is also produced in the failing human heart. One way to induce aldosterone synthesis in the heart would be to increase the expression of CYP11B2, the enzyme catalyzing the terminal step in aldosterone synthesis. However, CYP11B2 expression has never been examined in cardiac tissue from patients with heart failure. We assayed CYP11B2 expression in left ventricular tissue obtained at autopsy from seven patients. Total RNA was extracted from frozen samples. CYP11B2 gene expression was then quantitatively analyzed using a modified real-time PCR method that enabled assay of samples containing very small amounts of template DNA. The template DNA was initially amplified 1024-fold by subjecting it to 10 PCR cycles in the absence of the TaqMan probe. Thereafter, conventional real-time PCR was simultaneously performed on both target and standard samples. We measured the small quantities of CYP11B2 gene transcript and found the levels to be significantly higher in samples from heart failure patients than in those from cardiovascular disease-free patients. Our modified real-time PCR method enables quantitative analysis of gene expression using very small amounts of template DNA. CYP11B2 expression is up-regulated in the failing human heart.

Cytochrome P-450 CYP11B2↗

PubMed2001

Paraoxonase gene Gln192Arg (Q192R) polymorphism is associated with coronary artery spasm.

We recently reported that oxidative stress is involved in the pathogenesis of coronary spasm. We hypothesized that oxidative-stress-related genetic factors and certain polymorphisms in the paraoxonase gene (PON1) and platelet-activating factor acetylhydrolase (PAF-AH) might influence the pathogenesis of coronary spasm. We therefore examined the possible association between the PON1 Q192R or PAF-AH V279F polymorphisms and coronary spasm in 214 patients with coronary spasm and 212 control subjects. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism analysis. The incidence of the PON1-192R allele was significantly higher in the coronary spasm group than in the control group (65% vs 53%; P=0.0005). The PAF-AH-279F allele was not associated with coronary spasm (15% vs. 16%; P=0.8781). Multiple logistic regression analysis with forward stepwise selection involving the PON1-192R allele and the environmental risk factors revealed that the most predictive independent risk factor for coronary spasm was the PON1-192R allele (significance=0.0016, OR=2.52), followed by cigarette smoking (significance=0.0007, OR=2.01). We also measured plasma levels of TBARS (thiobarbituric acid-reactive substances) as a marker of oxidative stress. TBARS levels were higher in R/R types than in Q/Q types (2.115+/-0.086 nmol/ml [ n=25] vs 1.676+/-0.102 nmol/ml [ n=11], P<0.01). Thus, there is a significant association between the PON1-192R allele and coronary spasm; the PON1-192R allele may play an important role in the genesis of coronary spasm, probably by attenuating the suppression of oxidative stress.

Adult↗

PubMedDate not supplied

Cardiac displacement with a congenital complete left-sided pericardial defect in a patient with exertional angina pectoris--a case report.

A 71-year-old man with exertional chest pain was admitted to the hospital. A chest roentgenogram exhibited levoposition of the heart. An electrocardiogram showed clockwise rotation in the precordial leads and ST depression in V6, V7, V8, and V9 as well as in II, III, aVF leads associated with chest pain in a treadmill exercise test. The congenital complete left-sided pericardial defect could not be diagnosed preoperatively, but it was confirmed by thoracotomy.

Aged↗