Kazuhiko Hotta

Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with serum ACE concentration and increased risk for CAD in the Japanese.

BACKGROUND The angiotensin I-converting enzyme (ACE) is a key component of the renin-angiotensin system thought to be important in the pathogenesis of hypertension and cardiovascular disease. Deletion polymorphism in the ACE gene may be a risk factor for myocardial infarction in the Caucasian population. However, this finding has not yet been investigated in the Japanese population. METHODS AND RESULTS A 287-bp insertion/deletion polymorphism in intron 16 of the ACE gene was examined by polymerase chain reaction in a cross-sectional study of 100 healthy subjects and 178 patients with coronary artery disease (CAD) (70 angina pectoris, 108 myocardial infarction), whose serum ACE levels were concomitantly measured. Polymorphism of the ACE gene was characterized by three genotypes: two deletion alleles (genotype DD), two insertion alleles (genotype II), and heterozygous alleles (genotype ID). No differences could be detected among the three genotypes for total cholesterol, HDL cholesterol, and body mass index. Serum ACE levels were 11.4 +/- 2.7, 14.5 +/- 3.5, and 16.6 +/- 4.6 IU/mL for genotypes II, ID, and DD, respectively. In the study population, the genotype DD was more closely associated with CAD than the other two genotypes (ID and II). The frequency of deletion alleles was higher (0.58) in the CAD group than in healthy control subjects (0.42) (P < .05). Furthermore, multivessel disease was more strongly associated with deletion alleles than with insertion alleles (P < .05). CONCLUSIONS A deletion polymorphism of the ACE gene is associated with serum ACE activity and increased risk for CAD in the Japanese.

Estradiol-17β regulates the induction of VCAM-1 mRNA expression by interleukin-1β in human umbilical vein endothelial cells

Abstract We examined the effect of estradiol-17β on the expression of vascular cell adhesion molecule-1 (VCAM-1), an adhesion molecule, in human umbilical vascular endothelial cells. After preincubation with estradiol-17β for 24 hours, cells were treated for 4 h with 0.5 μg/ml recombinant human interleukin-1β. The RNase protection assay was performed using an [α-32P]-labeled 121 base pair VCAM-1 cRNA probe. Preincubation with estradiol-17β (250 or 500 pg/ml) suppressed the induction of VCAM-1 mRNA expression by interleukin-1β. VCAM-1 staining with a monoclonal antibody decreased when cells were incubated with estradiol-17β at 250 and 500 pg/ml, while staining was detectable when cells were treated with interleukin-1β at 0.5 μg/ml. In conclusion, estradiol-17β regulates the induction of VCAM-1 gene expression by interleukin-1β in human umbilical vein endothelial cells.

Effects of doxazosin on blood pressure and serum lipid levels in hypertensive patients

Abstract Eighteen hypertensive patients were treated with doxazosin, a selective alpha 1 -adrenergic inhibitor (1 to 2 mg daily), for 8 weeks. Mean systolic blood pressure was reduced from 174 ± 3 mm Hg to 154 ± 3 mm Hg at 8 weeks and diastolic blood pressure from 93 ± 2 mm Hg to 86 ± 2 mm Hg ( P P P P