Ribonucleic acid interference knockdown of interleukin 6 attenuates cold-induced hypertension.
Ribonucleic acid interference knockdown of interleukin 6 attenuates cold-induced hypertension.
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DOI：
10.1161/hypertensionaha.109.146902
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Sun Z
中科院分区：
文献类型：
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作者：
Crosswhite P;Sun Z
本研究的目的是确定促炎细胞因子IL-6在冷诱导高血压（CIH）中的作用。使用4组雄性Sprague道利大鼠（6只大鼠/组）。血压（BP）稳定后，3组分别接受携带IL-6shRNA的AAV、携带乱序shRNA的AAV（ScrshRNA）和磷酸盐缓冲溶液（PBS）的静脉内递送，然后暴露于冷环境（5°C）。最后一组接受PBS并保持在室温（25°C，温热）作为对照。AAV递送IL-6shRNA显著减弱了冷诱导的收缩压升高，并将其保持在对照水平长达7周（研究长度）。长期暴露于冷上调IL-6在主动脉，心脏和肾脏的表达和增加巨噬细胞和T细胞浸润的肾脏，表明冷暴露增加炎症。IL-6shRNA递送消除了冷诱导的IL-6上调，表明IL-6的有效沉默。有趣的是，IL-6的RNAi敲低预防了冷诱导的炎症，如通过IL-6shRNA完全抑制TNF-α表达和白细胞浸润所证明的。RNAi敲低IL-6显著降低了冷诱导的血管超氧化物产生的增加。值得注意的是，IL-6shRNA消除了冷诱导的心脏中胶原沉积的增加，表明炎症参与了冷诱导的心脏重塑。冷暴露导致肾小球塌陷，这可以通过敲低IL-6来防止，表明炎症在冷诱导的肾损伤中起重要作用。结论：冷暴露增加了IL-6的表达和炎症，这在CIH以及心脏和肾脏损伤的发病机制中发挥着关键作用。
The purpose of this study was to determine the role of the pro-inflammatory cytokine IL-6 in cold-induced hypertension (CIH). Four groups of male Sprague Dawley rats were used (6 rats/group). After blood pressure (BP) was stabilized, 3 groups received intravenous delivery of AAV carrying IL-6shRNA, AAV carrying scrambled shRNA (ScrshRNA), and phosphate buffered solution (PBS), respectively, prior exposure to a cold environment (5°C). The last group received PBS and was kept at room temperature (25°C, warm) as a control. AAV delivery of IL-6shRNA significantly attenuated cold-induced elevation of systolic BP and kept it at the control level for up to 7 weeks (length of the study). Chronic exposure to cold up-regulated IL-6 expression in aorta, heart and kidneys and increased macrophage and T-cell infiltration in kidneys, suggesting that cold exposure increases inflammation. IL-6shRNA delivery abolished the cold-induced up-regulation of IL-6, indicating effective silence of IL-6. Interestingly, RNAi knockdown of IL-6 prevented cold-induced inflammation as evidenced by a complete inhibition of TNF-α expression and leukocyte infiltration by IL-6shRNA. RNAi knockdown of IL-6 significantly decreased the cold-induced increase in vascular superoxide production. It is noted that IL-6shRNA abolished the cold-induced increase in collagen deposition in the heart, suggesting that inflammation is involved in cold-induced cardiac remodeling. Cold exposure caused glomerular collapses which could be prevented by knockdown of IL-6, suggesting an important role of inflammation in cold-induced renal damage. Conclusions: Cold exposure increased IL-6 expression and inflammation which play a critical role in the pathogenesis of CIH and cardiac and renal damage.