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Apr 12th  Key Note Lecture


Pablo_Nakagawa-photo 3 final.jpg

“Identification and characterization of the novel renin-expressing neurons in the nucleus ambiguus”


The role of the brain renin-angiotensin system (RAS) in blood pressure (BP) and autonomic control is recognized. However, the lack of the precise source of renin in the brain is one of the main barriers towards a complete understanding of how the brain RAS operates. Here, we hypothesized that renin is expressed in brain regions involved in sympathetic control such as the rostroventral lateral medulla (RVLM). We employed RNAscope, a highly sensitive and specific in situ hybridization technology. Surprisingly, the renin positive signals were absent in the RVLM, but we identified renin transcripts in the nucleus ambiguus (NA), a site in the vicinity of the RVLM that contains cardiac vagal motoneurons. There was no signal in this region with the negative control scrambled probe. The signal strength was greater than that observed in other regions of the brain classically associated with the brain RAS. We also observed that the NA contains other necessary RAS components to produce angiotensin. Interestingly, renin was colocalized with cells expressing choline acetyltransferase (ChAT), suggesting its possible role in cholinergic neurotransmission. Therefore, we generated mice lacking renin specifically in cholinergic neurons (Ren-aChAT-null). Because we previously identified an alternative brain-specific renin isoform (ren-b) that elicits cardioprotective roles, we also generated mice lacking ren-b in cholinergic neurons (Ren-bChAT-null). At baseline, Ren-aChAT-null exhibited a trend towards decreased BP, while Ren-bChAT-null exhibited higher BP, although these differences were not statistically significant. Importantly, Ren-aChAT-null exhibited an attenuated tachycardiac and pressor responses to atropine, indicating a lower parasympathetic tone in these mice. Conversely, Ren-bChAT-null exhibited an augmented pressor response to atropine suggesting an elevated parasympathetic tone. These data suggest that the activation of the brain RAS in the NA might play a role in cholinergic neurotransmission, and it defines the NA as a potential source of endogenous renin in the brainstem. Studies to understand the differential contribution of Ren-a and Ren-b in the NA to BP are in progress.

Pablo Nakagawa, PhD.
Medical College of Wisconsin
Dr. Pablo Nakagawa, PhD
Medical College of Wisconsin

03/2002 – 07/2008 BS/MS, University of Buenos Aires, Buenos Aires, Argentina
09/2010 – 04/2014 PhD,University of Buenos Aires, Buenos Aires, Argentina
12/2007 – 03/2008 Clinical Training in Biochemistry, Hematology, Hemostasis, and Parasitology, Evita Hospital, Buenos Aires, Argentina.
12/2006 – 02/2009 Undergraduate Research Fellow, Dept of Biological Chemistry, University of Buenos Aires, Buenos Aires, Argentina.
03/2009 – 06/2014 Predoctoral fellow, Dept of Internal Medicine, Division of Hypertension and Vascular research, Henry Ford Hospital, Detroit, MI.
07/2014 – 08/2016 Research Instructor/Scientist (mentored position), Dept of Internal Medicine, Division of Hypertension and Vascular research, Henry Ford Hospital, Detroit, MI.
09/2016 – 01/2019 Postdoctoral Fellow, Dept of Pharmacology, University of Iowa, Iowa City, IA
02/2019 – 06/2020 Postdoctoral Fellow, Dept of Physiology, Medical College of Wisconsin, Wauwatosa, WI
07/2020 – 12/2021 Instructor, Dept of Physiology, Medical College of Wisconsin, Milwaukee, WI
01/2022-current Assistant Professor, Medical College of Wisconsin, Milwaukee, WI 

男性にとってのハートブレイク:Loss of Y chromosomeと心不全の関連性

国立循環器病研究センター  佐野宗一


男性の血液中からY染色体が失われる「血液の後天的Y染色体喪失(Loss of Y

chromosome in leukocyte: LOY)」は、ヒトの体細胞変異の中でも最も一般的なもので、70歳になると40%以上に急激に増加する。LOYは、アルツハイマー病や固形がんなどの疾患リスクの増加と関連していることが以前から報告されていたが、その仕組みは不明だった。今回、私たちの研究によって、LOYのある男性では心不全など心臓病の経過が悪いことが明らかになり、動物実験によってその因果関係の一端が明らかになった。


2008年 大阪市立大学医学部卒業
2018年 大阪市立大学大学院医学研究科博士課程修了(総代)


2014年 ボストン大学ワイタッカー心血管研究所 ポストドクトラルアソシエート

2018年 バージニア大学心血管研究センター リサーチアソシエート
2019年 バージニア大学医学部心血管部門 アシスタントプロフェッサー

2021年 大阪市立大学大学院医学研究科循環器内科学 特任講師
2022年 大阪公立大学大学院医学研究科循環器内科学 特任講師(大学名変更)

2023年 国立循環器病研究センター 独立型研究室 室長

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