論文

Abstract Context Renal sinus fat (RSF) accumulation is associated with cardiometabolic diseases, such as obesity, diabetes, hypertension, and chronic kidney disease. However, clinical implications of RSF in primary aldosteronism (PA) remain unclear. Objective We aimed to investigate relationships between RSF volume and key cardiometabolic and renin-angiotensin system (RAS) parameters in PA patients and clarify the differences in these relationships between unilateral and bilateral subtypes. Methods We analyzed data obtained from well-characterized PA patients that involved 45 unilateral (median age: 52 years; 42.2% men) and 92 bilateral patients (51 years; 42.4% men). Results RSF volume normalized by renal volume (RSF%) was greater in the unilateral group than in the bilateral group (P < .05). RSF% was greater in men than in women (P < .05). RSF% positively correlated with parameters related to cardiometabolic risk, including age, body mass index, visceral fat volume, creatinine, triglycerides/high-density lipoprotein cholesterol ratio, uric acid, fasting glucose, and C-reactive protein regardless of PA subtypes (all P < .05). Intriguingly, RSF% positively correlated with plasma aldosterone concentration (PAC), aldosterone-to-renin ratio, and intact parathyroid hormone (iPTH) (all P < .05) in bilateral patients but did not correlate with RAS parameters and even showed an opposite trend in unilateral patients. In subgroup analyses by sex, these distinctions became more evident in women. After adjustment for potential confounders, RSF% remained positively correlated with PAC and iPTH in bilateral patients. Conclusion Our results indicate that RSF accumulation is involved in cardiometabolic dysfunction associated with PA. However, there were distinct correlations between RSF volume and RAS parameters according to sex and PA subtypes.

AbstractAll neuronal cells hold the same genetic information but vary by their structural and functional plasticity depending on the brain area and environmental influences. Such variability involves specific gene regulation, which is driven by transcription factors (TFs). In the field of neuroscience, epigenetics is the main mechanism that has been investigated to understand the dynamic modulation of gene expression by behavioral responses, stress responses, memory processes, etc. Nowadays, gene expression analyzed by real‐time quantitative PCR and TF binding estimated by chromatin immunoprecipitation (ChIP) enables one to dissect this regulation. Because of the wide range of transgenic models, as well as cost‐effective aspects, mouse models are widely used neuroscience. Thus, we have set up a protocol that allows extraction of both RNA for gene expression analysis and chromatin for ChIP experiment from a single mouse hippocampus. Using such protocols, information regarding gene expression and regulatory molecular mechanisms from the same animal can be integrated and correlated with neurobiological and behavioral outcomes. © 2021 Wiley Periodicals LLC.This article was corrected on 19 July 2022. See the end of the full text for details.Basic Protocol 1: Hippocampus isolation from mouse brainBasic Protocol 2: RNA extraction and gene expression analysis from a mouse half hippocampusBasic Protocol 3: ChIP from one hemisphere side mouse hippocampus

Background/Aims. Arterial stiffness is an independent risk factor for cardiovascular morbidity and mortality. This study was conducted to determine the effect of olmesartan (OLM) and azelnidipine (AZL) on arterial stiffness using the cardio-ankle vascular index (CAVI), which is a novel blood pressure (BP)-independent marker for arterial stiffness in hypertensive patients.Methods. Fifty-two consecutive hypertensive patients were randomly assigned either to a group treated with OLM monotherapy or to a group treated with OLM and AZL combination therapy. Clinical and biological parameters were measured before and 12 months after the start of this study.Results. Both therapies significantly and similarly reduced BP, augmentation index, and plasma aldosterone levels. The combination therapy significantly decreased CAVI and serum low-density lipoprotein (LDL-C) levels and these reductions were significantly greater than those produced with monotherapy. No significant differences in metabolic parameters were observed between the two therapies.Conclusion. The combination therapy with OLM and AZL had beneficial effects on arterial stiffness assessed by CAVI, LDL-C, and metabolism, despite the similar BP reduction, compared with OLM monotherapy. Since these markers are known to influence the future risk of cardiovascular events, combination therapy with OLM and AZL could be a useful choice for treating hypertensive patients.

The "preconditioning effect" in AKI is a phenomenon in which an episode of ischemia-reperfusion results in tolerance to subsequent ischemia-reperfusion injury. However, its relationship between DNA damage repair has not been elucidated. Here, we show the role of KAT5 in the preconditioning effect. Preconditioning attenuated DNA damage in proximal tubular cells with elevated KAT5 expression. Ischemia-reperfusion (IR) injuries were exacerbated, and preconditioning effect vanished in proximal tubular-cell-specific KAT5 knockout mice. Investigation of tubuloglomerular feedback (TGF) by MALDI-IMS and urinary adenosine revealed that preconditioning caused attenuated TGF at least in part via KAT5. In addition, K-Cl cotransporter 3 (KCC3) expression decreased in damaged proximal tubular cells, which may be involved in accelerated TGF following IR. Furthermore, KAT5 induced KCC3 expression by maintaining chromatin accessibility and binding to the KCC3 promoter. These results suggest a novel mechanism of the preconditioning effect mediated by the promotion of DNA repair and attenuation of TGF through KAT5.

Background/Aims: 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. Methods: One hundred consecutive hypertensive patients were randomly assigned either to a group treated with calcium channel blocker (CCB)-based therapy or a group treated with telmisartan-based therapy. Clinical and biological parameters were then measured before and 12 months after the start of this study. Results: CAVI, the logarithm of urinary albumin excretion, and BP were reduced significantly after telmisartan-based therapy. The decreases in 24-hour diastolic BP and daytime systolic BP associated with telmisartan-based therapy were significantly greater than those associated with CCB-based therapy. Both therapies significantly and similarly decreased the clinical BP, 24-hour systolic BP, daytime diastolic BP and serum levels of low-density lipoprotein cholesterol. No significant differences in the metabolic parameters were observed between the two therapies. Conclusion: Telmisartan-based therapy had beneficial effects on arterial stiffness assessed by CAVI, albuminuria, 24-hour BP and metabolism compared with CCB-based therapy. Since these markers are known to influence the future risk of cardiovascular events, telmisartan could be a useful drug for hypertensive patients.