Treg cells depletion is a mechanism that drives microvascular dysfunction in mice with established hypertension.
Treg cells depletion is a mechanism that drives microvascular dysfunction in mice with established hypertension.
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Treg 细胞耗竭是导致高血压小鼠微血管功能障碍的一种机制。
DOI：
10.1016/j.bbadis.2018.10.031
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Matrougui,Khalid
中科院分区：
文献类型：
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作者：
Radwan,Eman;Mali,Vishal;Haddox,Samuel;El-Noweihi,Amira;Mandour,Manal;Ren,Jun;Belmadani,Souad;Matrougui,Khalid
背景微血管功能障碍是高血压患者的主要并发症。我们以前报道过，CD 4 + CD 25+调节性T细胞（Treg）在高血压引起的血管功能障碍中起重要的预防作用。然而，Treg细胞治疗和自噬抑制是否可以挽救Treg细胞的存活和微血管功能，在建立的高血压是一个重要的问题，仍然没有答案。Methods & resultsHere，我们表明，Treg细胞从建立的高血压小鼠模型显示了增强的凋亡率，这是拯救与Treg细胞转移和自噬抑制。我们还发现，在建立高血压的小鼠肠系膜阻力动脉（MRA）中，自噬增加。重要的是，抑制自噬或将Treg细胞单次转移到已建立高血压的小鼠中可以独立于高血压改善微血管功能。这种保护作用涉及调节白细胞介素-10（IL-10）、炎症、内质网（ER）应激、氧化应激、Akt和eNOS.ConclusionsThe本研究表明Treg细胞的存活受自噬调节。此外，Treg细胞作为一种细胞疗法，旨在通过自噬依赖性机制拯救微血管功能，而不依赖于动脉血压降低作用。由于我们建立的高血压小鼠模型模拟了临床情况，我们的结果有可能用于新的治疗方法，包括操纵Treg细胞和自噬，以克服已建立的高血压诱导的心血管并发症。
BackgroundMicrovascular dysfunction is a major complication in hypertensive patients. We previously reported that CD4+CD25+T regulatory cells (Treg) play an important preventive role in hypertension-induced vascular dysfunction. However, whether Treg cells therapy and autophagy inhibition could rescue Treg cells survival and microvascular function in established hypertension is an important question that remained unanswered.Methods & resultsHere we showed that Treg cells from mice model of established hypertension displayed an enhanced apoptotic rate, which was rescued with Treg cells transfer and autophagy inhibition. We also showed increased autophagy in mesenteric resistance artery (MRA) in mice with established hypertension. Importantly, the inhibition of autophagy or one single transfer of Treg cells into mice with established hypertension improved the microvascular function independently of high blood pressure. The protection involves the modulation of interleukin-10 (IL-10), inflammation, endoplasmic reticulum (ER) stress, oxidative stress, Akt, and eNOS.ConclusionsThe present study suggests that Treg cells survival is regulated by autophagy. Also, Treg cells as a cellular therapy aimed at rescuing the microvascular function through an autophagy-dependent mechanism and independently of arterial blood pressure lowering effects. Because our mouse model of established hypertension mimics the clinical situation, our results have the potential for new therapeutic approaches that involve the manipulation of Treg cells and autophagy to overcome established hypertension-induced cardiovascular complications.