Hiromi Rakugi

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..These findings provide new insights into the mechanisms of Klotho action and support the therapeutic potential of membrane-form Klotho to regulate endothelial function...

..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...

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..This variant susceptibility may be caused by gene-environmental interactions and low birth weight in Asian populations...

..These findings suggest the possibility that amelioration of cerebrovascular dysfunction with an angiotensin receptor blocker could be a novel therapeutic strategy for the early stage of Alzheimer disease...

..However, studies with simultaneous measurement of mineral bone disorder (MBD)-related factors were scarce. This study aimed to identify factors predicting renal outcome independent of other factors...

..Poorer vitamin D status and higher CaP product might be partly responsible for functional and structural changes of vasculature, respectively, in DM...

..This parameter could provide additional information about renal arteriosclerotic change independent of estimated glomerular filtration rate and albuminuria, and should be considered a therapeutic target for renal protection...

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..003), with an odds ratio of 0.35 (95% confidence interval=0.17-0.76). Overall, the rs2290532 (D254N) polymorphism in OSBPL10 may predispose individuals with this SNP to hyper-LDL cholesterolemia...

..0332) by Cox's proportional hazard model. These data suggest that increased aortic stiffness and CKD may be predictors for stroke and cardiovascular events in hypertensive patients...

..Endogenous ACE2 in vascular cells may contribute to counteracting the Ang II-mediated cellular response partly by upregulating the Ang 1-7 signaling through Mas...

..Safety and tolerability will also be investigated. A total of more than 4000 patients were recruited and will be followed up for at least 3 years...

..Our findings suggest that Timp-3 may be a novel therapeutic target for the treatment of hypertension and consequent organ damage...

..However, the independent associations of these factors with cardiovascular disease (CVD), the leading cause of death among CKD patients, remain unclear. Our purpose was to identify which of these factors predict incident CVD in CKD...

..0011) prior to changeover were independently correlated with reduction in UPE. Our results suggest that the maximum dose of valsartan is more effective than the maximum dose of candesartan for reducing BP and proteinuria...

..Cerebrovascular changes and alteration in brain insulin signaling might play a pivotal role in this relationship. These findings could provide insights into this intensely debated association...

..The lack of a spontaneous animal model of NASH, however, has hampered basic research in this field...

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..Here, we examined whether HGF can protect against systemic inflammatory response syndrome induced by LPS and investigated the mechanism...

..We conclude that HGF reduced cardiac fibrosis by inhibiting endothelial-mesenchymal transition and the transformation of fibroblasts into myofibroblasts...

..Further development of the next generation of Ang II type 1 receptor blockers with added organ protective actions, such as PPARγ activation, might provide new beneficial drugs to treat renal and cardiovascular diseases...

..We evaluate the efficacy and safety of the maximal dose of candesartan administered to renal transplant patients...

..The renal-protective effect of ACE2 might involve more than just suppressing angiotensin II-mediated AT1 receptor signaling...

..In conclusion, our data suggested that C/A polymorphism in intron 13 of the HGF gene is associated with susceptibility to essential hypertension in lean or female subjects...

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..Our results suggest that the polymorphism of myospryn is associated with left ventricular hypertrophy, and an association between a Z-disc protein and cardiac adaptation in response to pressure overload...

..We previously reported that the vascular RAS activity is activated in vascular smooth muscle cells (SMC) by insulin stimulation. However, the effect of insulin on the RAS in endothelial cells (EC) is not fully understood...

..This study examined the association of mutations in adiponectin gene with the prevalence of coronary artery disease (CAD)...

..To clarify the contribution of this polymorphism to obesity and related conditions, we studied the association of the -866 G/A polymorphism of the UCP2 gene with obesity, hypertension and type 2 diabetes mellitus...

..0284) were correlated with reduction of urinary proteins during changeover. Taken together, our results suggest that benidipine may have greater efficacy than amlodipine in reducing blood pressure and proteinuria...

..Here, we studied whether klotho single nucleotide polymorphisms (SNP) were associated with carotid atherosclerosis...

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..However, little information is available about an effect of cigarette smoking on progression of primary kidney diseases, including immunoglobulin A (IgA) nephropathy...

..01), and most of them had hypertension. In contrast, the G276T polymorphism was not associated with adiponectin concentration or hypertension. In conclusion, hypoadiponectinemia is a marker for predisposition to hypertension in men...

..In this study, we investigated whether RI could be used to evaluate the pathogenesis of renal damage or the mechanisms of reduction of renal function by aging...

..While some reports suggest a relationship between hyperuricemia and chronic kidney disease (CKD), the renoprotective mechanism of an XO inhibitor in CKD remains unknown. Recent reports have focused on XO as a source of oxidative stress...

..Further studies will be necessary to evaluate the usefulness of benidipine combined with a β-blocker in terms of the incidence of stroke and new-onset diabetes in older patients...

..Here, we designed an in vitro study to test whether inhibitors of extracellular signal-regulated kinase and mitogen-activated kinase kinase could affect Klotho regulation of apoptosis and cellular senescence...

..We have identified a functional variant (-845A/G) of CYP4A11 that is significantly associated with hypertension and that appears to be a novel candidate for a predisposing factor for hypertension...

..Given these results, nephrologists should consider prescribing active vitamin D, especially for females and patients with diabetes, massive proteinuria, or secondary hyperparathyroidism...

..In summary, a severely hyperinsulinemic state may regulate VSMC and EC proliferation via activation of vasoactive substances such as ET-1 and nitric oxide induced by insulin...

..These data suggest that a quantitative measure of FMC, not supernatant or serum fetuin-A as measured in previous studies, reflects extraosseous calcification stress...

..05). These data suggested that two polymorphisms of different beta-adrenoreceptor subtypes are the genetic influences on the development of arterial stiffness and left ventricular hypertrophy in essential hypertension...

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..In conclusion, ACE2 protects against high-calorie diet-induced insulin resistance in mice. This mechanism may involve the transcriptional regulation of GLUT4 via an A1-7-dependent pathway...

..Since risk factors for atherosclerosis accelerate endothelial senescence and impair angiogenesis, we examined the role of Lp(a) in dysfunction and senescence of endothelial progenitor cells (EPC) and endothelial cells...

..Enhancing autophagy may provide a novel therapeutic option to minimize AKI...

..Enhancement of vasodilation and angiogenesis by sarpogrelate might provide a unique treatment for PAD and DM patients...

..These pleiotropic effects of antihypertensive drugs such as cilnidipine and carvedilol might provide additional benefits in the treatment of hypertensive postmenopausal women...

..0209). These three SNPs, especially the Trp64Arg SNP of β(3)ADR, might be risk factors for CVD in hypertensive patients...

..37, 95% CI: 1.02-1.85, p=0.025). Our findings demonstrate that the CRP level is independently associated with LVMI, and suggest that measurement of CRP may provide clinically important prognostic information to supplement LVH...

..Furthermore, our data indicate that the inhibition of Apop-1-induced death by IGF-1 is mediated by the activation of the PI3K/Akt signaling pathway...

..One SNP, rs1121980, and a haplotype of three SNPs in FTO that contains this SNP, might be important in the progression of insulin resistance in Japanese subjects...

..Thus, it is mandatory to develop novel therapy to prevent atherosclerosis in high Lp(a) concentration. Here, we focused on the effect of estrogen on Lp(a) level and Lp(a)-induced vascular remodeling...

..Furthermore, we investigated the prognostic impact of MIP-1beta on stroke and cardiovascular events in hypertensive patients in a small cohort study...

..We hypothesized that changes in serum asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and concomitant insulin resistance may be underlying factors connecting the two pathologic alterations...

..The downregulated genes include the polymeric Ig receptor (pIgR) which was reportedly involved in single nucleotide polymorphism (SNP) of Japanese IgAN patients...

..We examined the genetic involvement of the TSC gene in essential hypertension in Japanese...

..Therefore, it is suggested that ANG II antagonizes insulin-mediated production of PI(3,4,5)P(3) via a Ca(2+)-dependent but PKC-independent pathway in cardiac myocytes...

..It is still not clear which of or how these transcripts are involved in the pathogenesis of atherosclerosis...

..We examined whether nicorandil, a hybrid nitrate and adenosine triphosphate-sensitive potassium channel opener, could improve a biomarker and physiological markers of cardiovascular events...

..These findings might provide a novel diagnostic tool for AD using the elevation of plasma Abeta level after glucose loading...

..Taken together, both markers give us additional information that cannot be obtained just by using PTH, provided that we know the characteristics of these markers...

..In conclusion, we demonstrated that treatment with JJ316 has a dramatic therapeutic effect on an experimental crescentic glomerulonephritis, possibly due to expansion and activation of Treg cells...

..These results have important implications for the development of disease-modifying therapy for Alzheimer disease as well as understanding of Abeta metabolism...

..These results suggest that Klotho suppresses TNF-alpha-induced expression of adhesion molecules and NF-kappaB activation. Klotho may have a role in the modulation of endothelial inflammation...

..We conclude that the Fas promoter gene, SNP (-670G/A), may be a risk factor of MI occurrence...

..Disruption of this regulatory function may accelerate cardiac hypertrophy and shorten the transition period from compensated hypertrophy to cardiac failure...

..beta2- and beta3-adrenoceptor polymorphisms could predict the future BP elevation and further weight gain-induced BP elevation in originally obese subjects...

..In conclusion, increased aortic stiffness evaluated by PWV is more prognostic of cardiovascular events in hypertensive patients than several non-invasive atherosclerotic evaluations...

..The expression of p53 and p21 was lower in Klotho-treated cells. Our study suggests that Klotho acts as a humoral factor to reduce H(2)O(2)-induced apoptosis and cellular senescence in vascular cells...

..In conclusion, these data demonstrate that the deubiquitinating enzyme CYLD may inhibit inflammation and proliferation in vascular cells and may represent a novel target for the treatment or prevention of atherosclerosis...

..Thus, the DD genotype of ACE may be a genetic risk factor for cerebro-cardiovascular disease, especially cardiovascular events, in hypertensive patients in Japan...

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..We examined the association between MetS, CKD, and left ventricular hypertrophy (LVH), and prospectively investigated the predictive value of the combination of MetS and CKD for cardiovascular disease (CVD) in essential hypertension...

..Adiponectin concentration could be a marker of the existence of atherosclerosis, and measurement of its concentration may be helpful in assessment of the progress of atherosclerosis...

..Moreover, these renal protective effects were abrogated by a neutralizing antibody against HGF. Thus, the present study demonstrated that HGF counteracts the vicious cycle of Ang II-TGF-β1-AT(1)R, mediating the inhibition of PTEN...

..Our results suggest that activation of HF before waking and LF/HF during waking might play an important role in the development of morning blood pressure elevation...

..005). These results suggest that in evaluation of serum HGF concentration, the forearm vasodilator response to reactive hyperemia and PWV might be useful for managing hypertension in patients who are receiving antihypertensive therapy...

..Further investigation in a large-scale clinical trial is needed to determine the optimal target BP for LVH patients...

..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...

..Our observations suggest that hypoadiponectinemia is associated with impaired endothelium-dependent vasorelaxation and that the measurement of plasma adiponectin level might be helpful as a marker of endothelial dysfunction...

..Our results suggest that mouse membrane-form Klotho protein acts as a humoral factor to increase ACE activity in HUVEC via a cAMP-PKA-dependent pathway. These findings may provide a new insight into the mechanism of Klotho protein...

..Usefulness of inhibitors of the rennin-angiotensin system has been also reported in LIFE substudy and ANBP2. It is still required to perform large scale trials in the elderly hypertension to answer these undissolved problems...

..The association between UA and CVD events may be introduced in part because of a direct association of UA with LVMI...

..This interesting finding might suggest a feasible explanation for the huge interracial differences in the frequency of salt-sensitive hypertension...

..When treating hypertension in elderly patients, the approach should be to identify individual pathophysiological characteristics and lower the BP cautiously and slowly...

..These data suggest that autophagy maintains proximal tubule cell homeostasis and protects against ischemic injury. Enhancing autophagy may provide a novel therapeutic approach to minimize acute kidney injury and slow CKD progression...

..Eligible patients are being enrolled from May 2003 until May 2006. Results from the COPE trial should provide new evidence for selecting optimal combination therapies for hypertensive patients...

..Our findings, thus, indicate that the expression of Apop-1 induces apoptosis though CypD-dependent pathway and that Apop-1 plays roles in cell death under physiological conditions...

..Indeed, recent investigations revealed that several SNPs are involved in salt sensitivity or the efficacy of antihypertensive treatment. In this review, we would like to discuss the potential of personalized antihypertensive therapy...

..We conclude that CXCL12 secreted from stromal cells or podocytes acts on endothelial cells to regulate vascular development in the kidney. These findings suggest new potential therapeutic targets for remodeling the injured kidney...

..HYVET (hypertension in the very elderly) indicates that moderate and severe hypertension should be aggressively treated even those patients are 80 years or older, but evidence of antihypertensive treatment has not been clarified...

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..In conclusion, pratosartan is an effective and well tolerated antihypertensive drug, and may have beneficial effects on hypertensive patients with some metabolic disorders...

..This is the first reported case of exercise-induced AKI associated with RPLS. Vasoconstriction and endothelial dysfunction are considered as the common etiology of these diseases...