著者

Michiya Igase Yoshikazu Yonei Shigeru Matsumi Akihiko Shimode Tetsuya Maruyama Keiji Igase Maya Ohara Yoko Okada Masayuki Ochi Sayaka Matsumoto Yasumasa Ohyagi

出版者

Society for Glycative Stress Research

雑誌

Glycative Stress Research (ISSN:21883602)

巻号頁・発行日

vol.6, no.2, pp.75-81, 2019 (Released:2019-07-26)

著者

Kensuke Toyama Michiya Igase Joshua M. Spin Yasunori Abe Amarsanaa Javkhlant Yoko Okada Markus U. Wagenhäuser Hubert Schelzig Philip S. Tsao Masaki Mogi

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

vol.3, no.3, pp.170-177, 2021-03-10 (Released:2021-03-10)

参考文献数

23

被引用文献数

4

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Background:Tight junction (TJ) disruption and dysfunction are involved in the progression of arteriosclerosis. miR-501-3p regulates endothelial TJ protein-1, resulting in TJ disruption. Because exosomal microRNAs can travel to distant tissues and influence cell behavior, patients with elevated miR-501-3p may experience accelerated vascular disease progression secondary to miR-501-3p-induced reductions in TJ. This study investigated whether plasma exosome miR-501-3p levels are associated with vascular stiffness, an indicator for arteriosclerotic changes.Methods and Results:Fifty-one subjects (mean [±SD] age 70±8 years, 37% male) enrolled in a medical checkup program were recruited to the study. Brachial-ankle arterial pulse wave velocity (baPWV) and plasma exosome miR-501-3p expression were measured. Patients were divided into 2 groups depending on whether their miR-501-3p ∆Ctvalues were above (“High”; n=24) or below (“Low”; n=27) the cut-off levels determined by receiver operating characteristic (ROC) curve analysis. Median (interquartile range) baPWV levels were significantly higher in the miR-501-3p High than Low group (1,664 [1,496–1,859] vs. 1,450 [1,353–1,686] cm/s, respectively; P<0.05). Multivariate logistic regression analysis showed a significant association between increased baPWV and High miR-501-3p expression (odds ratio 4.66). At follow-up visits (mean 62 months later), baPWV remained significantly higher in the miR-501-3p High than Low group (1,830 [1,624–2,056] vs. 1,620 [1,377–1,816] cm/s, respectively; P<0.05).Conclusions:High expression levels of exosome miR-501-3p contribute to arteriosclerotic changes.

著者

Masanori A. Murayama Nagisa Arimitsu Jun Shimizu Naruyoshi Fujiwara Kenji Takai Yoko Okada Chieko Hirotsu Erika Takada Tomoko Suzuki Noboru Suzuki

出版者

Japanese Association for Laboratory Animal Science

雑誌

Experimental Animals (ISSN:13411357)

巻号頁・発行日

vol.70, no.3, pp.387-397, 2021 (Released:2021-08-06)

参考文献数

71

被引用文献数

1 6

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Elderly patients with dementia suffer from cognitive dysfunctions and neuropsychiatric symptoms (NPS) such as anxiety and depression. Alzheimer’s disease (AD) is a form of age-related dementia, and loss of cholinergic neurons is intimately associated with development of AD symptoms. We and others have reported that neural cell transplantation ameliorated cognitive dysfunction in AD model mice. It remains largely unclear whether neural cell transplantation ameliorates the NPS of AD. It would be interesting to determine whether NPS correlates with cognitive dysfunctions before and after neural cell transplantation in AD model mice. Based on the revalidation of our previous data from a Morris water maze test, we found that neural cell transplantation improved anxiety and depression significantly and marginally affected locomotion activity in AD mice. A correlation analysis revealed that the spatial learning function of AD mice was correlated with their NPS scores both before and after cell transplantation in a similar manner. In contrast, in the mice subjected to cell transplantation, spatial reference memory function was not correlated with NPS scores. These results suggested the neural cell transplantation in the AD model mice significantly improved NPS to the same degree as cognitive dysfunctions, possibly via distinct mechanisms, such as the cholinergic and GABAergic systems.

著者

Masanori A. Murayama Nagisa Arimitsu Jun Shimizu Naruyoshi Fujiwara Kenji Takai Yoshiki Ikeda Yoko Okada Chieko Hirotsu Erika Takada Tomoko Suzuki Noboru Suzuki

出版者

Japanese Association for Laboratory Animal Science

雑誌

Experimental Animals (ISSN:13411357)

巻号頁・発行日

vol.70, no.3, pp.398-405, 2021 (Released:2021-08-06)

参考文献数

61

被引用文献数

1 4

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Alzheimer’s disease (AD) is a prevalent neurological disorder affecting memory function in elderly persons. Indeed, AD exhibits abnormality in cognitive behaviors and higher susceptibility to neuropsychiatric symptoms (NPS). Various factors including aging, sex difference and NPS severity, are implicated during in development of AD. In this study, we evaluated behavioral abnormalities of AD model, PDAPP transgenic mice at young age using the Morris Water Maze test, which was established to assess hippocampal-dependent learning and memory. We found that female AD model mice exhibited spatial learning dysfunction and highly susceptible to NPS such as anxiety and depression, whereas spatial reference memory function was comparable in female PDAPP Tg mice to female wild type (WT) mice. Spatial learning function was comparable in male AD model mice to male WT mice. Multiple regression analysis showed that spatial learning dysfunction was associated with NPS severity such as anxiety and depression. Furthermore, the analysis showed that spatial reference memory function was associated with status of depression, but not anxiety. Thus, these results suggest female dominance of spatial learning dysfunction in the AD model mice accompanying increased NPS severity. The understandings of AD model may be useful for the development of therapeutic agents and methods in human AD.

著者

Hiroaki Ichimori Shigetoyo Kogaki Kunihiko Takahashi Hidekazu Ishida Jun Narita Nobutoshi Nawa Hiroki Baden Toshiki Uchikawa Yoko Okada Keiichi Ozono

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-12-0997, (Released:2013-05-18)

参考文献数

37

被引用文献数

5 8

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Background: To investigate the possible role of sex hormones in the pathogenesis of pulmonary arterial hypertension (PAH), the effect of β-estradiol (E2) on bone morphogenetic protein (BMP) signaling, a key signaling pathway involved in PAH, was studied in human pulmonary arterial endothelial cells (HPAEC). Methods and Results: BMP signaling molecules, including BMP receptor, Smad1/5/8 and Id1, were studied in HPAEC under 1% O2 (hypoxia) and 21% O2 (normoxia) as well as the effect of hypoxia-inducible factor (HIF)-1α expression in the presence of E2 on BMP signaling. The effects of an estrogen receptor (ER) antagonist (ICI 182,780) and cycloheximide, and the interaction of ER with Smad or HIF-1α were also studied. In the presence of E2, BMP signaling was augmented under normoxia but suppressed under hypoxia. HIF-1α accumulation suppressed BMP signaling, whereas HIF-1α inhibition augmented signaling. These effects were cancelled by ICI 182,780. Moreover, binding between ER, HIF-1α and phosphorylated (p)-Smad1/5/8 proteins occurred only under hypoxia. On inhibition of de novo synthesis with cycloheximide, however, p-Smad1/5/8 expression was suppressed only under normoxia. Conclusions: The effects of E2 on BMP signaling in HPAEC altered depending on O2 concentration and different mechanisms may be involved. BMP and sex hormones may play an important role in PAH development.