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Cirbp 抑制破坏了 DHODH 介导的铁死亡防御，减弱了老年供体移植模型中的低温心脏保护作用。

Cirbp suppression compromises DHODH-mediated ferroptosis defense and attenuates hypothermic cardioprotection in an aged donor transplantation model.

机构信息

Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center.

Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, National Children's Medical Center, and.

出版信息

J Clin Invest. 2024 Mar 12;134(9):e175645. doi: 10.1172/JCI175645.

DOI:10.1172/JCI175645
PMID:38690728
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11060748/
Abstract

Hypothermia is commonly used to protect donor hearts during transplantation. However, patients transplanted with aged donor hearts still have severe myocardial injury and decreased survival rates, but the underlying mechanism remains unknown. Because aged hearts are not considered suitable for donation, the number of patients awaiting heart transplants is increasing. In this study, we examined whether hypothermic cardioprotection was attenuated in aged donor hearts during transplantation and evaluated potential therapeutic targets. Using a rat heart transplantation model, we found that hypothermic cardioprotection was impaired in aged donor hearts but preserved in young donor hearts. RNA-Seq showed that cold-inducible RNA-binding protein (Cirbp) expression was decreased in aged donor hearts, and these hearts showed severe ferroptosis after transplantation. The young donor hearts from Cirbp-KO rats exhibited attenuated hypothermic cardioprotection, but Cirbp overexpression in aged donor hearts ameliorated hypothermic cardioprotection. Cardiac proteomes revealed that dihydroorotate dehydrogenase (DHODH) expression was significantly decreased in Cirbp-KO donor hearts during transplantation. Consequently, DHODH-mediated ubiquinone reduction was compromised, thereby exacerbating cardiac lipid peroxidation and triggering ferroptosis after transplantation. A cardioplegic solution supplemented with CIRBP agonists improved hypothermic cardioprotection in aged donor hearts, indicating that this method has the potential to broaden the indications for using aged donor hearts in transplantation.

摘要

低温通常用于在移植过程中保护供体心脏。然而，接受老年供体心脏移植的患者仍然存在严重的心肌损伤和生存率降低的问题，但潜在的机制尚不清楚。由于老年心脏不被认为适合捐赠，因此等待心脏移植的患者人数正在增加。在这项研究中，我们研究了低温心肌保护在移植过程中是否在老年供体心脏中减弱，并评估了潜在的治疗靶点。使用大鼠心脏移植模型，我们发现低温心肌保护在老年供体心脏中受损，但在年轻供体心脏中得到保留。RNA-Seq 显示冷诱导 RNA 结合蛋白 (Cirbp) 在老年供体心脏中的表达减少，这些心脏在移植后表现出严重的铁死亡。Cirbp-KO 大鼠的年轻供体心脏表现出低温心肌保护作用减弱，但在老年供体心脏中过表达 Cirbp 可改善低温心肌保护作用。心脏蛋白质组学显示 Cirbp-KO 供体心脏在移植过程中二氢乳清酸脱氢酶 (DHODH) 的表达显著降低。因此，DHODH 介导的泛醌还原受损，从而加剧心脏脂质过氧化并在移植后引发铁死亡。含有 CIRBP 激动剂的心脏停搏液可改善老年供体心脏的低温心肌保护作用，表明该方法有可能扩大使用老年供体心脏进行移植的适应证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/d882fb311c91/jci-134-175645-g027.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/d03528911ecf/jci-134-175645-g026.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/4f62d703f3a7/jci-134-175645-g028.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/db0ef9530867/jci-134-175645-g029.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/3bdb5a21cedd/jci-134-175645-g030.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/c1dafe2b4772/jci-134-175645-g031.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/ad728390d2ff/jci-134-175645-g032.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/4cb4dc99e44c/jci-134-175645-g033.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/e540b213fbaa/jci-134-175645-g034.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/c4e2b70a10d1/jci-134-175645-g035.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/d882fb311c91/jci-134-175645-g027.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/d03528911ecf/jci-134-175645-g026.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/4f62d703f3a7/jci-134-175645-g028.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/db0ef9530867/jci-134-175645-g029.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/3bdb5a21cedd/jci-134-175645-g030.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/c1dafe2b4772/jci-134-175645-g031.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/ad728390d2ff/jci-134-175645-g032.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/4cb4dc99e44c/jci-134-175645-g033.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/e540b213fbaa/jci-134-175645-g034.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/c4e2b70a10d1/jci-134-175645-g035.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8885/11060748/d882fb311c91/jci-134-175645-g027.jpg

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2
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J Am Coll Cardiol. 2022 Mar 22;79(11):1108-1123. doi: 10.1016/j.jacc.2021.11.064.
3
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铁死亡与心肌缺血再灌注损伤之间的相互作用：分子机制与潜在治疗靶点。
Eur J Med Res. 2025 Jul 21;30(1):643. doi: 10.1186/s40001-025-02851-6.
4
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5
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6
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