Telmisartan Lowers Elevated Blood Pressure in Psoriatic Mice without Attenuating Vascular Dysfunction and Inflammation
Telmisartan Lowers Elevated Blood Pressure in Psoriatic Mice without Attenuating Vascular Dysfunction and Inflammation
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替米沙坦降低银屑病小鼠升高的血压而不减轻血管功能障碍和炎症
DOI：
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发表时间：
2019
影响因子：
5.6
通讯作者：
S. Karbach
中科院分区：
文献类型：
--
作者：
J. Wild;Rebecca Schüler;Tanja Knopp;M. Molitor;Sabine Kossmann;T. Münzel;A. Daiber;A. Waisman;P. Wenzel;S. Karbach
背景：银屑病的特征是血管功能障碍、动脉高血压和心血管疾病风险增加。我们最近发现，皮肤驱动的白细胞介素（IL）-17A表达促进小鼠银屑病样疾病，这与血管炎症，血管功能障碍和高血压有关。由于建议银屑病患者强化降低风险因素，我们旨在阐明血管紧张素II受体1型（AT 1）拮抗剂替米沙坦在重度银屑病样皮肤病小鼠模型中的影响。方法和结果：在角质形成细胞特异性IL-17 A过表达的小鼠（K14-IL-17 Aind/+小鼠）中，通过尾袖体积描记法测量的血压升高在替米沙坦治疗后显著降低。重要的是，K14-IL-17 Aind/+小鼠接受替米沙坦治疗后，通过离体主动脉环等长张力研究评估的血管功能障碍、通过CD 45 + CD 11b+免疫细胞流式细胞术分析测量的血管炎症以及通过L-012增强化学发光评估的外周氧化应激水平升高均未减弱，持续性皮肤炎症也未减弱。结论：我们提供了第一个证据表明，通过AT 1阻断对实验性银屑病进行有效的降压治疗，但对我们的严重银屑病样皮肤病小鼠模型中的血管炎症和功能障碍没有任何影响。这表明，只要皮肤炎症持续存在，银屑病的血管功能和炎症可能不会减弱。
Background: Psoriasis is hallmarked by vascular dysfunction, arterial hypertension, and an increased risk for cardiovascular diseases. We have shown recently that skin-driven interleukin (IL)-17A expression promotes psoriasis-like disease in mice, and this is associated with vascular inflammation, vascular dysfunction, and hypertension. As an intensive risk-factor reduction is recommended for psoriasis patients, we aimed to elucidate the impact of the angiotensin II receptor type 1 (AT1) antagonist telmisartan in a mouse model of severe psoriasis-like skin disease. Methods and Results: Elevated blood pressure measured by tail-cuff plethysmography in mice with keratinocyte-specific IL-17A overexpression (K14-IL-17Aind/+ mice) was significantly reduced in response to telmisartan. Importantly, vascular dysfunction, as assessed by isometric tension studies of isolated aortic rings, vascular inflammation measured by flow cytometry analysis of CD45+CD11b+ immune cells, as well as the increased peripheral oxidative stress levels assessed by L-012-enhanced chemiluminescence were not attenuated by telmisartan treatment of K14-IL-17Aind/+ mice, nor was the persisting skin inflammation. Conclusion: We provide first evidence for an effective antihypertensive treatment in experimental psoriasis by AT1 blockade, but without any impact on vascular inflammation and dysfunction in our mouse model of severe psoriasis-like skin disease. This suggests that vascular function and inflammation in psoriasis might not be attenuated as long as skin inflammation persists.
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影响因子：
15.9
作者：
Haak, Stefan;Croxford, Andrew L.;Waisman, Ari
通讯作者：
Waisman, Ari
影响因子：
6.5
作者：
Croxford, Andrew L.;Karbach, Susanne;Waisman, Ari
通讯作者：
Waisman, Ari
DOI：
10.1016/j.jid.2018.09.021
发表时间：
2019-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Rebecca Schüler;A. Brand;Sabrina Klebow;J. Wild;F. Veras;Elisabeth Ullmann;S. Roohani;F. Kolbinger;Sabine Kossmann;C. Wohn;A. Daiber;T. Münzel;P. Wenzel;A. Waisman;B. Clausen;S. Karbach
通讯作者：
Rebecca Schüler;A. Brand;Sabrina Klebow;J. Wild;F. Veras;Elisabeth Ullmann;S. Roohani;F. Kolbinger;Sabine Kossmann;C. Wohn;A. Daiber;T. Münzel;P. Wenzel;A. Waisman;B. Clausen;S. Karbach
影响因子：
39.3
作者：
Mehta, Nehal N.;Azfar, Rahat S.;Gelfand, Joel M.
通讯作者：
Gelfand, Joel M.
影响因子：
10.9
作者：
Takeshita J;Wang S;Shin DB;Mehta NN;Kimmel SE;Margolis DJ;Troxel AB;Gelfand JM
通讯作者：
Gelfand JM