Microglia in the hypothalamic paraventricular nucleus sense hemodynamic disturbance and promote sympathetic excitation in hypertension.

Autor: Wei B; Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China., Cheng G; Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China., Bi Q; Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China., Lu C; Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China., Sun Q; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China., Li L; Department of Pharmacy, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou 310013, China., Chen N; Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China., Hu M; Department of Cardiology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310013, China., Lu H; Zhejiang University, University of Edinburgh Institute, Zhejiang University School of Medicine, Haining 314400, China., Xu X; Zhejiang Chinese Medical University, Hangzhou 310013, China; Department of Neurology, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou 310013, China., Mao G; Zhejiang Provincial Key Lab of Geriatrics, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China., Wan S; Brain Center, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou 310013, China., Hu Z; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou 310058, China; Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Gu Y; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou 310058, China; Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Zheng J; Key Laboratory for Biomedical Engineering of Ministrey of Education, Collage of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310013, China., Zhao L; Key Laboratory for Biomedical Engineering of Ministrey of Education, Collage of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310013, China., Shen XZ; Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Brain Center, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou 310013, China; Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310058, China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou 310013, China., Liu X; Department of Neurology, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou 310013, China. Electronic address: liuxiaoli1010@126.com., Shi P; Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou 310013, China. Electronic address: ship@zju.edu.cn.
Jazyk: angličtina
Zdroj: Immunity [Immunity] 2024 Sep 10; Vol. 57 (9), pp. 2030-2042.e8. Date of Electronic Publication: 2024 Aug 07.
DOI: 10.1016/j.immuni.2024.07.011
Abstrakt: Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not clear. Recent advances revealed that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels and found that microglia in the hypothalamic paraventricular nucleus (PVN), a sympathetic center, were early responders to hypertensive challenges. Vasculature analyses revealed that the PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology relative to other brain regions. As such, the PVN was susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. Mechanistically, ATP ligation to microglial P2Y 12 receptor was responsible for microglial inflammatory activation and the eventual sympathetic overflow. Together, these findings identified a distinct vasculature pattern rendering vulnerability of PVN pre-sympathetic neurons to hypertension-associated microglia-mediated inflammatory insults.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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