Inflammation, Lymphatics, and Cardiovascular Disease: Amplification by Chronic Kidney Disease.
Inflammation, Lymphatics, and Cardiovascular Disease: Amplification by Chronic Kidney Disease.
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DOI：
10.1007/s11906-022-01206-4
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发表时间：
2022-10
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
肾脏疾病是产生毒素和炎症因子的肠道微生物组的组成和代谢的强烈调节剂。这些有害因素的主要途径是血管和神经。虽然淋巴管负责间质液、大分子和细胞的清除，但对肾损伤是否以及如何影响肠淋巴网络知之甚少。肾损伤刺激肠道淋巴管生成，激活淋巴管内皮细胞，增加肠系膜淋巴流量。肾损伤动物的肠系膜淋巴液含有增加水平的细胞因子、免疫细胞、isoleuglandin（IsoLG）（一种高度反应性的二羰基）和载脂蛋白AI（apoAI）。IsoLG在肾损伤动物的回肠中增加，并且暴露于髓过氧化物酶的肠上皮细胞产生更多的IsoLG。IsoLG修饰的apoAI直接增加淋巴管收缩并激活淋巴管内皮细胞。通过羰基清除剂治疗抑制IsoLG可减少肾损伤动物的肠淋巴管生成。我们小组和其他人的研究表明，在肾脏、肠道和心脏之间的相互作用中存在一种新的介质（IsoLG修饰的apoAI）和一种新的途径（肠道淋巴网络）。肾损伤激活肠淋巴管生成，并通过与肠道产生的IsoLG有关的机制增加淋巴流量。这些数据确定了肾脏肠道-心脏轴中的新途径，并为肾脏疾病引起的肠道破坏提供了新的靶点，这可能会减轻肾功能损害的主要不良后果，即心血管疾病。
Kidney disease is a strong modulator of the composition and metabolism of the intestinal microbiome that produces toxins and inflammatory factors. The primary pathways for these harmful factors are blood vessels and nerves. Although lymphatic vessels are responsible for clearance of interstitial fluids, macromolecules, and cells, little is known about whether and how kidney injury impacts the intestinal lymphatic network. Kidney injury stimulates intestinal lymphangiogenesis, activates lymphatic endothelial cells, and increases mesenteric lymph flow. The mesenteric lymph of kidney-injured animals contains increased levels of cytokines, immune cells, isolevuglandin (IsoLG), a highly reactive dicarbonyl, and of apolipoprotein AI (apoAI). IsoLG is increased in the ileum of kidney injured animals, and intestinal epithelial cells exposed to myeloperoxidase produce more IsoLG. IsoLG-modified apoAI directly increases lymphatic vessel contractions and activates lymphatic endothelial cells. Inhibition of IsoLG by carbonyl scavenger treatment reduces intestinal lymphangiogenesis in kidney-injured animals. Research from our group and others suggests a novel mediator (IsoLG-modified apoAI) and a new pathway (intestinal lymphatic network) in the cross talk between kidneys and intestines and heart. Kidney injury activates intestinal lymphangiogenesis and increases lymphatic flow via mechanisms involving intestinally generated IsoLG. The data identify a new pathway in the kidney gut–heart axis and present a new target for kidney disease-induced intestinal disruptions that may lessen the major adverse consequence of kidney impairment, namely cardiovascular disease.
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影响因子：
5.4
作者：
Abernethy A;Raza S;Sun JL;Anstrom KJ;Tracy R;Steiner J;VanBuren P;LeWinter MM
通讯作者：
LeWinter MM
影响因子：
--
作者：
Liakopoulos V;Roumeliotis S;Gorny X;Dounousi E;Mertens PR
通讯作者：
Mertens PR
DOI：
10.1080/00365510801930626
发表时间：
2008-01-01
影响因子：
2.1
作者：
Kals, Jaak;Kampus, Priit;Zilmer, Mihkel
通讯作者：
Zilmer, Mihkel
影响因子：
4.7
作者：
Boutaud, O;Ou, JJ;Oates, JA
通讯作者：
Oates, JA
影响因子：
3.7
作者：
Hill NR;Fatoba ST;Oke JL;Hirst JA;O'Callaghan CA;Lasserson DS;Hobbs FD
通讯作者：
Hobbs FD