Sustained elevation of NF-κB activity sensitizes offspring of maternal inflammation to hypertension via impairing PGC-1α recovery.
Sustained elevation of NF-κB activity sensitizes offspring of maternal inflammation to hypertension via impairing PGC-1α recovery.
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NF-κ B 活性持续升高通过损害 PGC-1 α 恢复使母体炎症后代对高血压敏感
DOI：
10.1038/srep32642
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发表时间：
2016-09-12
影响因子：
4.6
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Deng Y;Zhang Q;Luo H;Chen X;Han Q;Wang F;Huang P;Lai W;Guan X;Pan X;Ji Y;Guo W;Che L;Tang Y;Gu L;Yu J;Namaka M;Deng Y;Li X
越来越多的证据表明，母亲的有害因素，包括炎症，有助于高血压的发展在后代。目前的研究发现，在第二个学期接受脂多糖（LPS）刺激的产前炎症暴露的后代显示收缩压显著升高。此外，这些后代还显示出增强的血管损伤和活性氧（ROS）水平时，与醋酸脱氧皮质酮和高盐饮食（DOCA盐）的挑战，在胸部动脉瘤。有趣的是，抗氧化剂N-乙酰-L-半胱氨酸明显逆转了这些变化。从机制上讲，产前LPS暴露导致预先存在的过氧化物酶体增殖物激活受体-γ共激活因子（PGC）-1α升高，PGC-1 α是ROS代谢的关键主人，其上调ROS防御能力，并维持静息状态下ROS产生和消除的平衡。然而，持续升高的NF-κB活性显著抑制了接受产前炎症刺激的后代对DOCA-盐攻击的PGC-1α表达反应的快速恢复。通过使用NF-κB抑制剂（N-对甲苯磺酰基-L-苯丙氨酸氯甲基酮）恢复PGC-1α恢复并防止DOCA盐诱导的血压升高，进一步证实了这一点。我们的研究结果表明，母体炎症编程倾向于NF-κB过度激活，这损害了PGC-1α介导的抗氧化能力，导致后代对高血压损害的敏感性增加。
Growing evidence has demonstrated that maternal detrimental factors, including inflammation, contribute to the development of hypertension in the offspring. The current study found that offspring subjected to prenatal exposure of inflammation by lipopolysaccharide (LPS) challenge during the second semester showed significantly increased systolic blood pressure. In addition, these offspring also displayed augmented vascular damage and reactive oxygen species (ROS) levels in thoracic aortas when challenged with deoxycorticosterone acetate and high-salt diet (DOCA-salt). Interestingly, the antioxidant N-acetyl-L-cysteine markedly reversed these changes. Mechanistically, prenatal LPS exposure led to pre-existing elevated peroxisome proliferators-activated receptor-γ co-activator (PGC)-1α, a critical master of ROS metabolism, which up-regulated the ROS defense capacity and maintained the balance of ROS generation and elimination under resting state. However, continued elevation of NF-κB activity significantly suppressed the rapid recovery of PGC-1α expression response to DOCA-salt challenge in offspring that underwent prenatal inflammatory stimulation. This was further confirmed by using a NF-κB inhibitor (N-p-Tosyl-L-phenylalanine chloromethyl ketone) that restored PGC-1α recovery and prevented blood pressure elevation induced by DOCA-salt. Our results suggest that maternal inflammation programmed proneness to NF-κB over-activation which impaired PGC-1α-mediated anti-oxidant capacity resulting in the increased sensitivity of offspring to hypertensive damage.
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影响因子：
6.5
作者：
Kim, MS;Shigenaga, JK;Grunfeld, C
通讯作者：
Grunfeld, C
产前炎症诱导的 NF-κB 稳态失衡导致肾素-血管紧张素系统过度活跃，导致后代出现产前程序性高血压
影响因子：
4.6
作者：
Deng Y;Deng Y;He X;Chu J;Zhou J;Zhang Q;Guo W;Huang P;Guan X;Tang Y;Wei Y;Zhao S;Zhang X;Wei C;Namaka M;Yi P;Yu J;Li X
通讯作者：
Li X
影响因子：
15.8
作者：
Gravett CA;Gravett MG;Martin ET;Bernson JD;Khan S;Boyle DS;Lannon SM;Patterson J;Rubens CE;Steele MS
通讯作者：
Steele MS
影响因子：
7.4
作者：
Bruin, Jennifer E.;Petre, Maria A.;Holloway, Alison C.
通讯作者：
Holloway, Alison C.
影响因子：
10.8
作者：
Alvarez-Guardia, David;Palomer, Xavier;Vazquez-Carrera, Manuel
通讯作者：
Vazquez-Carrera, Manuel