Biomedical subjects

Kei Kamide

Publications and source records attributed to Kei Kamide.

43 records · Page 3Linked to original sources

PubMed2003

Association between left ventricular diastolic dysfunction and renal hemodynamic change in patients with treated essential hypertension.

The heart and kidneys are important target organs in hypertension. Early signs of hypertensive target organ damage can be detected by evaluating left ventricular (LV) diastolic function and intrarenal hemodynamics using Doppler ultrasonography. However, it has not been sufficiently clarified whether cardiac damage and renal impairment progress in parallel, especially from the early stage. In the present study, Doppler echocardiography and renal Doppler ultrasonography were performed in 99 patients with treated essential hypertension, and LV diastolic filling parameters, ie., the velocity ratio of atrial filling to early diastolic filling (A/E), and the deceleration time of the E wave (DcT) and renal Doppler parameters, i.e., the diastolic to systolic ratio (D/S) and resistance index (RI), were determined. D/S was negatively correlated and RI was positively correlated with A/E and DcT. These cardiac and renal Doppler parameters were also associated with age, diastolic blood pressure, creatinine clearance, and/or glucose levels. By multiple regression analysis, D/S was found to have a significant association with DcT, independent of other clinical parameters, including age. In subgroup analysis in which patients were divided by their glucose tolerance, a significant correlation between renal Doppler parameters and LV diastolic function was observed in subjects with normal glucose tolerance, but this correlation disappeared in those with impaired glucose tolerance and diabetes mellitus. The present findings show that there is a significant relation between LV diastolic function and renal Doppler parameters in treated hypertensive patients, and suggest that cardiac damage progresses in parallel with renal involvement in these patients from the early stage.

Aged↗

PubMed2002

Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity.

von Willebrand factor (VWF) is synthesized primarily in vascular endothelial cells and secreted into the plasma as unusually large VWF multimers. Normally, these multimers are quickly degraded into smaller forms by a plasma metalloproteinase, VWF-cleaving protease (VWF-CP). Decreases in the activity of this enzyme result in congenital and acquired thrombotic thrombocytopenic purpura (TTP). The human VWF-CP has recently been purified. Cloning of the corresponding cDNA revealed that the 1,427-aa polypeptide is a member of the ADAMTS gene family, termed ADAMTS13. Twelve rare mutations in this gene have been identified in patients with congenital TTP. Here, we report missense and nonsense mutations in two Japanese families with Upshaw-Schulman syndrome, congenital TTP with neonatal onset and frequent relapses. The comparison of individual ADAMTS13 genotypes and plasma VWF-CP activities indicated that the R268P, Q449stop, and C508Y mutations abrogated activity of the enzyme, whereas the P475S mutant retained low but significant activity. The effects of these mutations were further confirmed by expression analysis in HeLa cells. Recombinant VWF-CP containing either the R268P or C508Y mutations was not secreted from cells. In contrast, Q449stop and P475S mutants were normally secreted but demonstrated minimal activity. Genotype analysis of 364 Japanese subjects revealed that P475S is heterozygous in 9.6% of individuals, suggesting that approximately 10% of the Japanese population possesses reduced VWF-CP activity. We report on a single-nucleotide polymorphism associated with alterations in VWF-CP activity; it will be important to assess this single-nucleotide polymorphism as a risk factor for thrombotic disorders.

ADAM Proteins↗

PubMed2002

Verification of 525 coding SNPs in 179 hypertension candidate genes in the Japanese population: identification of 159 SNPs in 93 genes.

Single-nucleotide polymorphisms (SNPs) located in coding regions (coding SNPs; cSNPs) with amino acid substitution can potentially alter protein function. Therefore, identification of the nonsynonymous cSNPs of the genes of common diseases is valuable in tests of association with phenotypes. In this study, we validated 525 candidate cSNPs from 179 hypertension candidate genes deposited in the publicly available database dbSNP by DNA sequencing of samples from 32 Japanese individuals. We identified a total of 143 SNPs (27%) in 93 hypertension candidate genes. We also identified 16 new SNPs, for a total of 159 SNPs. Of the 159 SNPs thus identified, 104 were nonsynonymous. We estimate that approximately 20% of the SNPs deposited in dbSNP database showed a minor allele frequency of over 5%. The candidate SNPs for hypertension identified in this study would be valuable for association studies with hypertension to accelerate the identification of hypertension genes.

Gene Frequency↗

PubMed2002

Vascular signaling pathways in the metabolic syndrome.

There are several potential cellular and molecular pathways whereby cardiovascular risk factors act through very specific signal transduction pathways in the formation of atherosclerosis, as seen often in the metabolic syndrome. Many examples point to multiple postreceptor defects in the insulin signaling pathway in vascular tissue, however, there are differences in the insulin receptor pathway in vascular tissue compared with skeletal muscle or fat. In addition to insulin receptors, insulin may affect atherosclerotic changes in the vascular cells via stimulation of insulin-like growth factor-1 receptors and their signaling pathway. Insulin also causes activation of the vascular renin-angiotensin system in both vascular smooth muscle cells and endothelial cells. Insulin-activated tissue renin-angiotensin system leads to increased cell growth and contributes to the cause of atherosclerosis. The fact that agents that inhibit the renin-angiotensin system also block insulin-mediated renin-angiotensin system expression and cell growth reinforces the potential implication of a vascular insulin-renin-angiotensin system pathway. Finally, novel substances such as the adipokines, factors produced from fat cells, reveal new risk factors in the metabolic syndrome and offer further evidence for a link between insulin resistance and accelerated atherosclerosis.

Animals↗

PubMed2002

The renin-angiotensin and adrenergic nervous system in cardiac hypertrophy in fructose-fed rats.

BACKGROUND: Hyperinsulinemia and insulin resistance are associated with left ventricular hypertrophy (LVH) and cardiovascular complications in hypertensive subjects. The aim of this study was to explore the mechanisms for LVH including activation of the renin-angiotensin system system (RAS) and the sympathetic nervous system and their activation by insulin using a rat model of hyperinsulinemia and insulin resistance. METHODS: Male Sprague-Dawley rats were fed a high-fructose or control diet. The fructose-fed rats (FFR) were divided into four subgroups that were administrated either vehicle or the following antihypertensive drugs (n = 6-8) for 4 weeks: 1) olmesartan, an angiotensin II type 1 (AT1) receptor antagonist; 2) bunazosin, an alpha1-receptor blocker; and 3) hydralazine, a direct vasodilator. RESULTS: Fructose feeding induced significant increases in mean systolic blood pressure (BP) levels at 4 weeks (control, 117 v fructose, 131 mm Hg), left ventricular weight, and the sum of the insulin level in response to a glucose tolerance test (2 g/kg). Fructose feeding also increased urinary excretion of epinephrine and norepinephrine, the density of cardiac alpha1-adrenergic receptors, and the content of angiotensin II in the left ventricle. All antihypertensive drugs decreased systolic BP, but only the AT1 receptor antagonist attenuated the development of LVH in FFR. The AT1 receptor antagonist did not affect glucose-mediated insulin responses, but did suppress urinary catecholamine excretion and cardiac alpha1-adrenergic receptor density. CONCLUSIONS: Left ventricular hypertrophy in FFR may be less dependent on systemic elevations of BP and more dependent on the RAS and the sympathetic nervous system. Use of an AT1 receptor antagonist might be the most beneficial way to prevent progression of LVH through direct effects on tissue RAS and the sympathetic nervous system in FFR. As these changes occur in a rat model with hyperinsulinemia, insulin may have a role in promoting LVH by activating the local RAS and sympathetic nervous system activity.

Adrenergic alpha-Antagonists↗

PubMed2002

Decreases in serum uric acid by amelioration of insulin resistance in overweight hypertensive patients: effect of a low-energy diet and an insulin-sensitizing agent.

BACKGROUND: Hyperuricemia and hyperinsulinemia/insulin resistance are commonly seen in obese subjects and hypertensive patients. To clarify whether the insulin resistance plays a role in hyperuricemia, we investigated alterations in serum uric acid (UA) concentrations during treatment with a low-energy diet or an insulin-sensitizing agent in overweight hypertensive patients. METHODS: Twenty-eight overweight hypertensive patients (14 men and 14 women, mean age 61 +/- 2 years) were assigned to a weight reduction program with a low-energy diet (3360 kJ/day for 3 weeks, n = 14) and to treatment with troglitazone (200 mg twice daily for 8 weeks, n = 14). Measurements of body weight, blood pressure (BP), serum UA, and a 75-g oral glucose tolerance test were performed at baseline and the end of the intervention periods. RESULTS: Body weight and BP decreased significantly in the diet group but not in the troglitazone group at the end of the intervention periods. Levels of blood glucose, plasma insulin, and homeostasis model assessment-insulin resistance index (HOMA-R) improved similarly in the two groups. Serum UA concentration decreased by treatment both in the diet (0.4 +/- 0.2 mg/dL, P < .05) and troglitazone groups (1.0 +/- 0.2 mg/dL, P < .001). CONCLUSIONS: The amelioration of insulin resistance by either a low-energy diet or troglitazone decreased the serum UA level in overweight hypertensive patients. Insulin resistance or hyperinsulinemia, independent of body weight and BP, may play an important role in UA metabolism in multiple risk factor syndrome.

Adult↗

PubMed2002

Hypertension attenuates the efficacy of hypoglycemic therapy for preserving coronary flow reserve in patients with type 2 diabetes.

Impairment of coronary flow reserve (CFR) in patients with type 2 diabetes has been generally demonstrated; however, there have been few studies investigating CFR in cases of relatively well-controlled diabetes, in distinction to the influence of hypertension. The purpose of the present study was to evaluate the influence of diabetes and hypertension upon CFR in relatively well-controlled patients. This study included 12 healthy controls (C group) and 57 patients with type 2 diabetes (DM) and/or essential hypertension who were divided into three groups as follows: patients with DM (DM group; n = 24), patients with essential hypertension (HT group; n = 15), and patients with both DM and essential hypertension (DM+HT group; n = 18). We excluded patients with evidence of coronary artery disease and/or left ventricular hypertrophy. We performed transthoracic Doppler recording of diastolic coronary flow velocity (CFV) in the left anterior descending coronary artery at rest and after maximal vasodilation by adenosine infusion (140 microg/kg/min for 3 min) CFR was defined as the ratio of hyperemic to averaged basal peak CFV. The CFR (2.92 +/- 0.46) of the DM group was not decreased compared to that of the C group (2.96 +/- 0.58), although the CFR of the HT (2.33 +/- 0.25) and DM+HT (2.35 +/- 0.25) groups were significantly reduced. Left ventricular mass index, relative wall thickness, and diastolic function were worse in the HT and DM+HT groups than in the C and DM groups. Subjects with concentric left ventricular remodeling had a lower CFR than those with normal left ventricular geometry. In conclusion, adequate hyperglycemic control prevented the progression of coronary microcirculatory disturbance, but concomitant hypertension attenuated the effect.

Adenosine↗