Atsuhiro Ichihara

..A significant role of (pro)renin receptor in the pathogenesis of end-organ damage has been suggested only in animal studies. This study was conducted to examine the mRNA expression of (pro)renin receptor in human artery...

..These results suggest that long-term use of fluvastatin by hyperlipidaemic hypertensive patients is associated with a significant reduction in aortic stiffness without any effect on BP...

..The mechanism and substances causing nonproteolytic activation of prorenin may serve as important therapeutic targets for the prevention of diabetic organ damage...

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..In conclusion, untreated hypertensive patients with a higher 24-h ambulatory systolic BP variability had stiffer arterial walls. Ambulatory systolic BP variability may be involved in stiffening of the arteries of hypertensive patients...

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..It is not only AngII but also intraglomerular activation of MAPK by the receptor-associated prorenin that plays a pivotal role in diabetic nephropathy...

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..These studies clearly demonstrated that nonproteolytic activation of prorenin in glomeruli is critically involved in renal tissue RAS activation, leading to renal damage in hypertensive animals...

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..Thus, the (pro)renin receptor may be upregulated in podocytes under hypertensive conditions and may contribute to the breakdown of the glomerular filtration barrier...

..The antiatherogenic pleiotropic properties of amlodipine have a preventive effect on the progression of arterial stiffness in hypertensive patients treated with an ARB...

..We studied the preventive effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on arterial PWV values in this population...

..2+/-6.4% and 59.5+/-4.4%, respectively). These results suggest that AT1A receptors enhance tubuloglomerular feedback-mediated afferent arteriolar constriction, at least in part, through reducing the counteracting modulation by nNOS...

..Thus, (pro)renin-receptor blockade can be a useful therapy for chronic kidney disease with low renin levels in the plasma...

..Receptor-bound prorenin may prove useful as an important therapeutic target for the prevention and regression of end-organ damage in patients with diabetes...

..This study sought to compare the strength of predictions of arterial fibrosis by using a new parameter, the cardio-ankle vascular index (CAVI), versus pulse wave velocity (PWV) in patients with kidney failure treated with hemodialysis...

..To determine the long-term effects of intensive blood pressure (BP) lowering by antihypertensive drug therapy on aortic stiffness assessed by PWV, a single-blind randomized prospective study was performed...

..Long-term treatment with an ARB may decrease PRA in part by diminishing the storage of active renin in JG cells...

..Consequently, renin, prorenin and the (pro) renin receptor may be important therapeutic targets for the prevention and regression of nephropathy in patients with diabetes and/or hypertension...

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..These results indicate the significant contribution of RAPS to CNV pathogenesis...

..Because (P)RR is present in the podocytes, a central component of the glomerular filtration barrier, we hypothesized that aliskiren influences the (P)RR-induced two pathways in human podocytes...

..The aim of the present study was to define the association of the RAPS with diabetes-induced retinal inflammation...

..The purpose of the present study was to investigate whether nonproteolytically activated prorenin plays a role in ischemia-induced retinal neovascularization...

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..Our results suggest that transient high-dose angiotensin receptor blocker treatment effectively induced sustained regression of glomerulosclerosis by a mechanism mediated, in part, by changes in MMP-2 activity...

..Thus, (pro)renin receptor contributes to the accelerated pathogenesis in the heart and kidneys of diabetic SHRsp...

..Conversely, developmental exposure to Ang II during this "critical" period had the opposite effect, predisposing rats to higher blood pressure, renal injury, and oxidative stress after L-NAME administration...

..These results suggest that 12 months of add-on treatment with either amlodipine or hydrochlorothiazide could have beneficial effects in nondiabetic chronic kidney disease stage 1/2 patients already being treated with valsartan...

..Collectively, the DDAH2/ADMA pathway can be a novel therapeutic target for vasculopathy in the ADMA or angiotensin II-induced pathophysiological conditions...

..Recent clinical studies have shown that plasma NP levels were lower in subjects with the metabolic syndrome. The present study was conducted to elucidate the roles for NP/cGK cascades in energy metabolism...

..The QTL on rat chromosome 1 was primarily related to the postsynaptic response of RVLM bulbospinal neurons to brain angiotensin II, whereas both the QTL and other genomic regions influenced the basal activity of RVLM neurons...

..In conclusion, the findings suggest that treatment with valsartan, even at a low dose, may ameliorate some glycation and oxidative stress markers independently of an effect on blood pressure in hypertensive type 2 diabetic subjects...

..Candesartan may be a better antihypertensive drug than CCBs to improve subclinical atherosclerosis of patients with MetS...

..The (pro)renin receptor-mediated ERK signal transduction is thus a possible new therapeutic target for preventing vascular complications...

..This study clearly provided in vivo evidence for the AngII-independent MAPK activation by human (pro)renin receptor and induction of glomerulosclerosis with increased TGF-beta1 expression...

..These findings indicate that NF-YC functions as a new corepressor of agonist-bound MR via alteration of aldosterone-induced MR conformation...

..CONCLUSION: Add-on candesartan functionally improved the stiffened arteries of hypertensive patients treated with CCBs by the end of 12 months of treatment independently of its effects on BPs...

..The results explain the mechanism by which Ang II in the RVLM area increases peripheral sympathetic activity and blood pressure...

..C-reactive protein (CRP) expression is increased with metabolic alterations. We sought to clarify the effect of CRP on the development of obesity-induced metabolic disorders using human CRP-overexpressing transgenic mice (CRPTG)...

..In the present study, we investigated whether the combination of CRP and adiponectin is associated with further metabolic abnormalities compared to each of them alone...

..This study was conducted to determine the effect of telmisartan on the cardio-ankle vascular index (CAVI), a novel blood pressure (BP)-independent marker for arterial stiffness in hypertensive patients...

..Pressure-induced inhibition of prorenin processing in JG cells via phospholipase D-dependent pathways is enhanced in late diabetes...

..These results suggest that the ((P)RR)-dependent activation of prorenin contributes to the pathogenesis of slowly progressive nephropathy in the intact kidney in a rat model of renovascular hypertension...

..These results showed the physiological roles of Ubc9 and PIAS1 as SF-1 coactivators beyond sumoylation enzymes in adrenocortical steroidogenesis and suggested their possible pathophysiological roles in human cortisol-producing adenomas...

..Furthermore, it was suggested longitudinally that measuring HMW adiponectin is efficient to predict the progression to metabolic syndrome compared with measuring total adiponectin or HMW-total adiponectin ratio...

..The small G protein, Rho, and its downstream effector Rho-kinase have been shown to be involved in the tissue fibrosis process. This study was undertaken to investigate the role of Rho-kinase in the pathogenesis of these alterations...

..The objective of this study was to evaluate the relation between the genotypes of the MCP-1 A-2518G polymorphism and the development of carotid atherosclerosis in patients with type 2 diabetes...

..Renal Sirt1 can be a potential therapeutic target for the treatment of AKI...

..The objective of this study was to determine the effects of olmesartan medoxomil, a novel ARB, on the plasma level of BNP in hypertensive patients with type 2 diabetes...

..To investigate the role of individual MMPs, we examined the course of Adriamycin-induced albuminuria and glomerulosclerosis in mice lacking either a gelatinase (MMP-9) or a collagenase (MMP-13)...

..These findings demonstrate that nonproteolytically activated prorenin plays a significant role in the ocular inflammation and neovascularization...

..5. The results of the present study suggest that the improvement in proteinuria following eplerenone treatment is independent of its effects on sodium balance and may be mediated by effects on the expression of slit diaphragm proteins...

..A truncated form of (P)RR, termed M8.9, was also found to be associated with the vacuolar H(+)-ATPase (V-ATPase), implicating a non-RAS-related function of ATP6AP2...

..In contrast, excess ROS upregulates Sirt1, which activates FoxO3a and catalase leading to rescuing apoptosis. Thus, Sirt1 constitutes a determinant of renal tubular cell apoptosis by regulating cellular ROS levels...

..Thus, inhibition of Rho-Rho-kinase signaling may provide a therapeutic strategy for disrupting a vicious cycle of adipocyte stretch, Rho-Rho-kinase signaling, and inflammation of adipose tissue that contributes to and aggravates obesity...

..Thus, the L/HCTZ tablet could be a useful drug for Japanese diabetic patients with hypertension...

..These results suggest that ANA causes afferent arteriolar dilation via both CB1 and non-CB1 receptors and greater efferent arteriolar dilation via CB1 receptors, resulting in a decreased GFR and an increased RBF without affecting MAP...

..Based upon these results, we propose that anti-whole GAD65-reactive T cells have the ability to regulate the development of type 1 diabetes...

..68 g/day) within six months without any significant side effects. This case suggests that CsA monotherapy is effective for the treatment of both liver dysfunction and membranous nephropathy associated with PBC...

..We questioned whether the ratio of C-reactive protein to high-molecular-weight adiponectin (C/A ratio), compared to each value alone, is more useful to predict insulin resistance and/or metabolic syndrome...

..The level of beta cell dysfunction in GDM was associated with the severity of glucose intolerance and total insulin dosage required. These findings underpin clinical significance of beta cell dysfunction in GDM...

..Estrogen replacement therapy reversed the ovariectomy-induced changes. CONCLUSION: Estrogen-dependent COX-2 expression plays an important role in the RBF regulation in female rats...

..The FOXP3/Scurfin gene is known to be a master gene of Tregs. Therefore, we tried to analyze the relation between the gene polymorphism and adult onset type 1 diabetes and its subtype in the Japanese population...

..This study investigated whether the slope of estimated GFR is different between nonproteinuric subjects with and without diabetes, and what clinical factors are associated with the GFR slope...

..The inverse correlation between adiponectin and insulin resistance may manifest in the later phase of obesity development...

..In conclusion, the prorenin receptor is important for the maintenance of normal podocyte structure and function...

..maltophilia. For pneumonia due to S. maltophilia, new generation fluoroquinolones can be the treatment of choice, although S. maltophilia-related pneumonia should be treated very carefully because of its high fatality rate...

..These results suggest that (pro)renin receptor blockade does not only inhibit the progression of nephropathy but also reverses the glomerulosclerosis that has already developed in diabetic rats...

..Blockade of angiotensin (Ang) II has been shown to prevent new-onset type 2 diabetes. We focused on the effects of AngII on muscle mitochondria, especially on their biogenesis, as an underlining mechanism of type 2 diabetes...

..05). Within JSH 2009 Classes I, II and III, a shift in BP from a low to a high class between 16 and 20 weeks of gestation predicts the subsequent development of PIH...

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..The present study suggests the potential use of HRP, a decoy peptide binding to the prorenin receptor, as a therapeutic agent to reduce ocular inflammation...

..These results indicate that transmural pressure inhibits renin secretion via PLC-dependent pathways and prevents conversion of inactive renin to active renin via PLD-dependent mechanisms in JG cells...

..Renal biopsy revealed nodular and diffuse glomerulosclerosis characteristic of diabetic nephropathy. The present case demonstrates that nodular glomerulosclerosis may be present without clinically overt diabetes mellitus...

..Further inquiry regarding podocyte (P)RR intracellular signal transduction will be needed to develop a new therapeutic approach targeting podocyte (P)RR in patients with diabetic nephropathy...

..Thus prorenin also contributes to the development of nephropathy in type II diabetes, probably through a (pro)renin receptor-dependent mechanism...

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..To investigate the metabolic phenotype and pregnancy outcomes of gestational impaired glucose tolerance (IGT) defined by isolated hyperglycemia during an oral glucose tolerance test (OGTT)...

..Thus, the strategy for hypertension treatment with CCBs has entered a new era: treatment selection depends not only on blood pressure control but also on the subtypes of CCBs...

..Our study indicates that among CPR measurements, postprandial CPR index is the best predictive marker for future insulin therapy...

..The purpose of this study was to examine whether factors associated with arterial stiffness contributed to the development of CVD in patients with ESRD...

..These results suggest that changes in the renal microvasculature may have an important role in the mechanisms of hypertension prevention and regression by ARB...

..This negative regulation of NF-kappaB activation by Celecoxib might be an important mechanism leading to its anti-inflammatory activity...

..Taken together, licochalcone A might contribute to the potent anti-inflammatory effect of G. inflata through the inhibition of IKK activation...

..We investigated whether or not "low dose" metformin could prevent weight gain induced by pioglitazone...

..We investigated the efficacy of epalrestat, an aldose reductase inhibitor, for diabetic peripheral neuropathy in Japanese patients with type 2 diabetes...

..Therefore, the present case is thought to be unique because he was a normotensive patient with normal plasma renin activity and the renal arterial branch was only dissected...

..Thus, the (P)RR is a multi-functional molecule that shows the complex structure and behaviour. This review highlights the current insights and the future perspectives in research regarding the (P)RR and mammalian V-ATPase...

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..The (pro)renin receptor may prove useful as an important therapeutic target for the prevention and regression of end-organ damage in diabetes and hypertension...

..Thus, assessment of the ratio of renin to prorenin is needed to evaluate the significance of (pro)renin receptor...

..ODC protein was suggested to increase in compensation for the inhibition of its activity. Impaired ODC activity and polyamine production in the kidney may exaggerate salt-sensitive hypertension in SS rats...

..This is the first study to show an association between ALDH2 genetic polymorphisms and ACV elimination rate (t(1/2)) in Japanese end-stage renal disease patients...