Abstract 17317: Psoriasis and Vascular Dysfunction in Mice and Patients
Introduction: Interleukin-17A (IL-17A) is a central cytokine in psoriasis, an inflammatory skin disease connected to increased cardiovascular mortality. We searched for this correlation in our psoriasis patients and tried to find out in a mouse experimental approach if dermal over-production of IL-17A leading to skin inflammation has systemic side effects and evokes vascular dysfunction in psoriasis. We checked if treatment of psoriasis by biological agents blocking downstream of IL-17A also affects cardiovascular disease in mice and humans.
Methods and Results: Mice over-expressing IL-17A in keratinocytes were compared with the healthy controls. Dermal IL-17A over-expression lead to a severe psoriasis-like skin inflammation. We found an increased cardiovascular reactive oxygen species (ROS) formation (chemiluminescence, oxidative microtopography), serum levels of IL-17A and IL-6 and circulating CD11b+ inflammatory leukocytes (ELISA, flow cytometry). Psoriasis mice showed an increased systolic blood pressure, a compensatory heart hypertrophy and suffered from a vascular dysfunction. Immunohistochemistry and flow cytometry revealed in psoriatic mice an increased vascular production of the nitric oxide/superoxide reaction product peroxynitrite and infiltration of neutrophil granulocytes accompanied by increased expression of the inducible NO-Synthase and the NADPH oxidase subunit nox2 (Western Blot).
There was a significant correlation between psoriasis and cardiovascular disease in individuals with psoriasis compared to matched controls without psoriasis. Skin inflammation and ROS levels in blood of psoriatic mice were attenuated by anti-TNFα and anti-IL-6 treatment (histology, chemiluminescence). Under biological treatment with anti-TNFα or anti-IL-12p40, the skin affection improved significantly in psoriasis patients, accompanied by a significant improvement in low-flow-mediated constriction (L-FMC), suggesting an activation of the resting endothelial function in response to anti-inflammatory therapy.
Conclusion: Dermal over-expression of IL-17A does not only directly promote psoriatic plaque formation but may be also responsible for the induction of systemic cardiovascular disease.
- © 2013 by American Heart Association, Inc.