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Open AccessArticle

Telmisartan Lowers Elevated Blood Pressure in Psoriatic Mice without Attenuating Vascular Dysfunction and Inflammation

1
Center for Cardiology—Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany
2
Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, 55131 Mainz, Germany
3
German Center for Cardiovascular Research (DZHK)—Partner site Rhine-Main, 60590 Frankfurt, Germany
4
Institute of Molecular Medicine, University Medical Center Mainz, 55131 Mainz, Germany
5
Heart Research Institute, 2042 Sydney, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(17), 4261; https://doi.org/10.3390/ijms20174261
Received: 13 July 2019 / Revised: 24 August 2019 / Accepted: 28 August 2019 / Published: 30 August 2019
(This article belongs to the Special Issue Endothelial Dysfunction: Pathophysiology and Molecular Mechanisms)
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. View Full-Text
Keywords: psoriasis; vascular dysfunction and inflammation; Interleukin-17A; hypertension and anti-hypertensive treatment; telmisartan psoriasis; vascular dysfunction and inflammation; Interleukin-17A; hypertension and anti-hypertensive treatment; telmisartan
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Wild, J.; Schüler, R.; Knopp, T.; Molitor, M.; Kossmann, S.; Münzel, T.; Daiber, A.; Waisman, A.; Wenzel, P.; Karbach, S.H. Telmisartan Lowers Elevated Blood Pressure in Psoriatic Mice without Attenuating Vascular Dysfunction and Inflammation. Int. J. Mol. Sci. 2019, 20, 4261.

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