Evidence of specific inflammatory condition in nucleus tractus solitarii of neurogenic hypertension
Evidence of specific inflammatory condition in nucleus tractus solitarii of neurogenic hypertension
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神经源性高血压孤束核特定炎症状况的证据
DOI：
10.1113/expphysiol.2009.047324
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发表时间：
2010
期刊：
影响因子：
2.7
通讯作者：
Paton JF
中科院分区：
文献类型：
--
作者：
Waki H;Gouraud S;Maeda M;Paton JF
由于孤束核（NTS）是调节动脉压设定点的关键区域，我们提出了它在神经源性高血压发展中的作用。最近的研究表明，与血压正常的大鼠相比，促炎分子，如连接粘附分子1（JAM-1）在人类原发性高血压动物模型（自发性高血压大鼠（SHR））的NTS中高度表达（Wistar-Kyoto，WKY）。此外，我们还发现内源性白细胞积聚在SHR而非WKY大鼠NTS的毛细血管内。基于这些证据，我们假设细胞因子/趋化因子的基因表达在SHR的NTS中改变。我们使用RT 2 Profiler PCR阵列筛选了SHR NTS中异常表达的炎症介质，该阵列专门针对主要细胞因子/趋化因子。特异性PCR芯片显示，与WKY大鼠相比，7个基因在SHR NTS中表达减少（超过2倍），而只有2个基因在SHR中表达增加。此外，我们发现，这些验证的分子中的一些表现出重要的功能作用，心血管稳态的NTS水平。我们认为，促炎分子（如JAM-1）的异常基因表达导致SHR NTS血管内白细胞积聚。因此，特异性细胞因子/趋化因子的基因表达可能被下调，以避免SHR NTS中进一步强烈的炎症活性，代价是导致心血管自主神经病理学的神经元活性的改变。重要的是，为了翻译我们的工作，这些新的见解需要在高血压人类脑干组织中进行评估;它们的确认可能会导致世界上最流行的疾病之一的新治疗方法。
Since the nucleus tractus solitarii (NTS) is a pivotal region for regulating the set‐point of arterial pressure, we proposed a role for it in the development of neurogenic hypertension. Recent studies have suggested that proinflammatory molecules, such as junctional adhesion molecule 1 (JAM‐1) are highly expressed in the NTS of an animal model of human essential hypertension, the spontaneously hypertensive rat (SHR), compared with normotensive rats (Wistar–Kyoto, WKY). Moreover, we have also shown endogenous leukocyte accumulation inside capillaries within the NTS of SHR but not WKY rats. Based on this evidence, we hypothesized that gene expression of cytokines/chemokines is altered in the NTS of SHR. We have screened for abnormally expressed inflammatory mediators in the NTS of SHR using the RT2 Profiler PCR arrays, which were designed specifically to target major cytokines/chemokines. The specific PCR array revealed that seven genes were less expressed in the NTS of SHR compared with WKY rats (more than twofold differences), while only two genes were more expressed in the SHR. Moreover, we identified that some of these validated molecules exhibit important functional roles for cardiovascular homeostasis at the level of the NTS. We suggest that abnormal gene expression of proinflammatory molecules, such as JAM‐1, causes leukocyte accumulation within the vasculature in the NTS of SHR. Consequently, gene expression of specific cytokines/chemokines may be downregulated to avoid further strong inflammatory activity in the NTS of SHR at the expense of an alteration in neuronal activity that leads to cardiovascular autonomic pathology. Importantly, to allow translation of our work, these novel insights need to be assessed in hypertensive human brainstem tissue; their confirmation could lead to novel therapeutic approaches for one of the world's most prevalent diseases.