Biomedical subjects

Michitaka Tsuzuki

Publications and source records attributed to Michitaka Tsuzuki.

5 recordsLinked to original sources

PubMed2005

Inverse correlation between soluble CD40 ligand and soluble CD40 is absent in patients with unstable angina.

The CD40/CD40 ligand (CD40L) system mediates inflammatory processes important in atherogenesis and plaque instability. The expression of CD40L on activated T cells was suppressed by soluble CD40 (sCD40) in vitro. However, the relationship between soluble CD40L (sCD40L) and sCD40 in unstable angina (UA) is still unknown. Thirty-seven consecutive patients with recent chest pain or discomfort were recruited. Patients with both Braunwald's class IB-IIIB and with coronary stenosis (or stenoses) of >75% were assigned to the UA group (n = 19, aged 67.2 +/- 8.2 years), and the rest to the control group (n = 18, aged 63.4 +/- 8.7 years). The serum levels of sCD40L and sCD40, and the plasma levels of matrix metalloproteinase (MMP)-9, were measured by enzyme-linked immunosorbent assays. A significantly inverse correlation between sCD40L and sCD40 was shown in the controls (r = -0.72, P = 0.0007), but was absent in the UA group (r = -0.16, P not significant), although there was no statistical significance between these groups in terms of serum levels of sCD40L or sCD40. The difference of the regression slopes of these regression lines was statistically significant (P < 0.01). Additionally, there was a significant correlation between sCD40 and plasma levels of MMP-9 in the patients with and without UA (r = 0.58, P = 0.0096), but no significant correlation between sCD40L and MMP-9 levels (r = 0.00, P not significant). The balance between CD40 and CD40L may be lost in patients with UA. Soluble CD40 expression may also be related to MMP-9 expression in atherosclerotic tissues.

Aged↗

PubMed2004

Association of plasminogen activator inhibitor-1 4G/5G gene polymorphism with variations in the LDL particle size in healthy Japanese men.

BACKGROUND: Several studies have supported the association between a predominance of small, dense low-density lipoprotein (LDL) and the risk of coronary artery disease. As another potentially atherogenic factor, impaired fibrinolytic activity due to increased plasminogen activator inhibitor-1 (PAI-1) concentrations has been shown. In addition, the 4G allele of the 4G/5G polymorphism in the promoter region of the PAI-1 gene is reported to be associated with the atherogenic lipid profile. We investigated the relation between the PAI-1 gene polymorphism and LDL particle size. METHODS: A total of 156 healthy Japanese male subjects were recruited. The diameter of LDL particles was determined at their peak size using polyacrylamide gels using fresh plasma samples. RESULTS: Fasting insulin and triglyceride concentrations were found to be significantly higher, and the LDL particle size was smaller in the homozygotes for the 5G allele than in the carriers of the 4G allele. An analysis of covariance (ANCOVA) adjusting for insulin and triglyceride concentrations showed a consistently significant difference in LDL particle size between the two groups. In the forward stepwise multiple regression analysis, triglycerides, insulin, and the PAI-1 5G/5G genotype remained in the model as independent and significant predictors capable of influencing the LDL particle size. CONCLUSIONS: Our findings suggest that the 4G/5G polymorphism of the PAI-1 gene might be associated with LDL particle size in healthy Japanese males.

Adult↗

PubMed2003

The polymorphism of the beta3-adrenergic receptor gene is associated with reduced low-density lipoprotein particle size.

People with a predominance of small, dense low-density lipoprotein (LDL) particles appear to be at increased risk for coronary disease, independent of LDL cholesterol levels. The Trp64Arg variant of the beta3-adrenergic receptor gene is reported to be associated with abdominal obesity and resistance to insulin, and as a consequence, this variant may be a genetic factor in the development of atherosclerosis. Therefore, we investigated whether the beta3-adrenergic receptor polymorphism contributes to the distribution of LDL particle size in 136 Japanese subjects, aged 33 to 59 years, who visited for a routine annual checkup. None of these subjects were taking any medication. The diameter of LDL particles was determined at their peak size using nondenaturing 2% to 16% polyacrylamide gradient gels using fresh plasma samples. The genotype frequencies were: Trp/Trp, 71.3%; Try/Arg, 22.1%; and Arg/Arg, 6.6%, with allele frequencies of 0.82 for Trp64 and 0.18 for Arg64. The subjects with the Arg/Arg genotype had significantly higher levels of fasting plasma insulin and triglycerides and an insulin resistance index of homeostasis model assessment (HOMA-R), and significantly smaller LDL particle size than did the subjects with the Trp/Trp genotype. After adjusting for fasting insulin, body mass index (BMI), and HOMA-R index, there was no longer an observed difference in LDL particle size. The number of the Arg64 allele in individuals was significantly related with fasting insulin, BMI, triglycerides, glycosylated hemoglobin (HbA1c), and fasting glucose, and it was inversely related with LDL particle size. After adjusting for triglyceride, fasting insulin levels, and HOMA-R index, LDL particle size was no longer inversely correlated with the Arg allele. These findings suggest that the Trp64Arg variant in the beta3-adrenergic receptor gene may be associated with reducing LDL particle size, probably due to insulin resistance.

Adult↗

PubMed2003

Inhibition of COX-2 prevents hypertension and proteinuria associated with a decrease of 8-iso-PGF2alpha formation in L-NAME-treated rats.

BACKGROUND: The inhibition of nitric oxide (NO) exerts injurious effects on the cardiovascular system by several mechanisms, such as the activation of the renin-angiotensin system, oxidative stress, and inflammatory cytokines. We examined whether COX-2, an inducible isoform of cyclooxygenase, is associated with the pathogenesis observed in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. METHODS: Three groups of 8-week-old male Sprague-Dawley rats were studied (n = 6 in each group): group 1, untreated controls; group 2, treated with L-NAME (1 g/l for 3 weeks, p.o.); and group 3, L-NAME co-treated with COX-2 inhibitor NS-398 (5 mg/kg per day, i.p.). The L-NAME-induced expression of COX-2 mRNA and protein was semi-quantified in the kidneys and the thoracic aorta. Urinary excretion of the prostaglandin 6-keto PGF(1alpha), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) was measured in the three groups. Moreover, urinary excretion of 8-iso-PGF(2alpha), a potent vasoconstricting arachidonic acid metabolite acting through thromboxane A (TXA) receptor activation, proposed recently as a marker of oxidative stress, was also measured. RESULTS: L-NAME induced significant increases in systolic blood pressure (P< 0.01), urinary protein (P< 0.05), and renal excretion of 8-iso-PGF(2alpha)(P< 0.01), compared with the control. In L-NAME-treated rats, the levels of COX-2 mRNA and protein were more than 50% higher in the kidneys (P< 0.05), and six-fold higher in the thoracic aorta (P< 0.01) than in control rats. NS-398 significantly ameliorated an increase in systolic blood pressure (P< 0.01) and urinary protein (P< 0.05) induced by L-NAME. CONCLUSIONS: These data indicate that an increase in COX-2 expression might have a hypertensive effect, partly associated with 8-iso-PGF(2alpha) formation in l-NAME-treated rats.

Animals↗

PubMed2002

Quinapril prevents restenosis after coronary stenting in patients with angiotensin-converting enzyme D allele.

Restenosis after coronary artery stent implantation is attributed chiefly to intimal hyperplasia, which is prevented experimentally by angiotensin-converting enzyme (ACE) inhibitors. Therefore, the present study investigated whether the effect of quinapril, a tissue-specific ACE inhibitor, on the prevention of coronary restenosis differs according to ACE polymorphism. One hundred consecutive patients with successful stent implantation were randomly assigned to quinapril and control groups. Both follow-up angiography and ACE polymorphism analysis were obtained from 92 patients (control, 46; quinapril treatment, 46). The prevalence of risk factors did not differ statistically according to quinapril treatment or ACE genotypes. There was no statistically significant difference in the occurrence of restenosis 6 months after stenting between the groups. Quantitative coronary angiography revealed that quinapril treatment resulted in significantly higher minimal lumen diameter and significantly lower percent diameter stenosis (22.9 +/- 22.6 vs 37.1 +/- 19.7% in the control group, p < 0.05) in patients with the D allele although there was no difference in those with the II genotype. In addition, intravascular ultrasound revealed that quinapril treatment significantly prevented the loss of minimal lumen cross-sectional area and the increase in percent area stenosis (34.5 +/- 14.0 vs 53.3 +/- 16.4% in the control group, p < 0.05) in patients with the D allele compared to those with the II genotype. These results suggest that the administration of ACE inhibitors for the attenuation of lumen loss after coronary stent implantation is best for subjects with the D allele of the ACE genotype.

Aged↗