Perirenal adipose tissue derived exosomes regulate blood pressure in rats
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1. Department of Physiology of Binzhou Medical University, Yantai 264003, China. 2. Weihai Central Blood Station, Weihai 264200

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R-33

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    Abstract:

    Objective To investigate whether perirenal adipose tissues as an endocrine organ regulate arterial blood pressure in rats via exosomes. Methods Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used in this study. Perirenal fat of normotensive WKY rats and SHRs was cultured in serum-freeidentified by nano-size measurement, transmission electron microscopy, and surface markers, which were consistent with the characteristics of exosomes (Exo) and used for subsequent experiments. SHR and WKY rats were randomly divided into two groups and injected with Exo-SHR or Exo-WKY via the tail vein once a week for 6 weeks. Arterial blood pressure was measured while rats were conscious using a non-invasive caudal cuff system. Acute experiments were conducted at the end of week 6 after the injection of exosome-like vesicles. Carotid artery cannulation was used to directly measure arterial blood pressure. HE and Masson staining was used to observe cardiovascular pathological remodeling. Peripheral sympathetic tone (PST) was expressed as the relative ratio of the depression response induced by intravenous injection of hexamethonium hydrochloride to that in WKY rats treated with Exo-WKY. Exosomes labeled with PKH67 green fluorescent dye were injected into the tail vein for in vivo tracing, and then incubated with primary cultured neurons for in vitro tracing. Results Exosomes secreted from perirenal white adipose tissue were typical exosome semi-cup-like vesicles under transmission electron microscopy. The average diameter of nanoparticles was approximately 100 nm, and surface-specific markers TSG101 and CD9 were expressed. The systolic blood pressure (SBP) of SHRs began to decrease in the second week after injection of Exo-WKY and remained low throughout experiment (P< 0. 05). Exo-WKY also decreased the crosssectional area of cardiomyocytes, aortic media thickening, and PST in SHRs (P< 0. 05). However, after administering Exo-SHR to WKY rats, no significant changes were observed in SBP, the cross-sectional area of cardiomyocytes, media thickness of the aorta, or PST. Green fluorescence was observed in the cardiovascular center, including the PVH, nucleus tracts solitary, rostral ventrolateral medulla, and in cultured neurons at 24 h after application of PKH67-labeled exosomelike vesicles. Conclusions Perirenal adipose tissue-derived exosomes act as transport carriers to remotely regulate arterial blood pressure. Exo-SHR lack contents that inhibit blood pressure elevation. Exo-WKY supplementation reduces arterial blood pressure and sympathetic tension, which improves cardiovascular remodeling.

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History
  • Received:September 04,2022
  • Revised:
  • Adopted:
  • Online: April 13,2023
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