Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02087-y

The autoimmune skin disease psoriasis and its associated cardiovascular comorbidity – a multifaceted problem

J. Wild1, J. Ringen2, T. Bieler2, T. Knopp2, J. Lagrange2, M. Molitor3, K. Sies4, A. Kropp5, K. Keller1, A. Daiber6, T. Münzel1, M. Rauh5, A. Waisman7, P. Wenzel3, J. Titze8, S. Karbach3, für die Studiengruppe: AG 4

1Kardiologie 1, Zentrum für Kardiologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; 2Centrum für Thrombose und Hämostase, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; 3Zentrum für Kardiologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; 4Klinik für Dermatologie, Uniklinik Heidelberg, Heidelberg; 5Department of Pediatrics and Adolescent Medicine, Uniklinik Erlangen, Erlangen; 6Labor für Molekulare Kardiologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; 7Institute of Molecular Medicine, University Medical Center Mainz, Mainz; 8Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Germany, Singapore, SG;

Background: The Interleukin-17A driven autoimmune skin disease psoriasis is known to be associated with cardiovascular disease: Psoriasis patients are patients of high cardiovascular risk even if they do not exhibit any other cardiovascular risk factor besides their autoimmune disease. We found vascular inflammation in a genetic murine IL-17A driven psoriasis model as possible reason for vascular dysfunction(1). Besides, we have previously detected alterations in the body's water balance forcing a catabolic response to prevent dermal dehydration as new mechanism to explain hypertension in this genetic murine psoriasis model(2). We now investigated our concept in short term drug-induced imiquimod (IMQ)-driven psoriasis. Methods: We treated C57BL/6J mice with IMQ, assessed skin water loss, blood pressure, physical activity and heart rate. We performed metabolic cage studies and analysed vascular function/inflammation and oxidative stress. Results: After 5 days of IMQ-treatment, mice lost almost 70% of their total body water through the skin. In parallel, urine excretion was nearly completely abolished. IMQ-treated mice prevented renal water loss by renal vasoconstriction and reduced osmotic diuresis. High intra-renal urea levels provided osmotic force for urine concentration under IMQ. After initial peak, blood pressure and heart rate dropped on day 3 and then normalized. Within this time, the acute skin disease turned into a chronic, compensated state. On day 10, IMQ-treated mice showed vascular inflammation. Conclusion: Skin barrier disruption by IMQ provoked acute cutaneous water loss and a fast compensatory whole-body response. Our data suggest similar urea-depending water conservation mechanisms in acute as in long-term experimental psoriasis. These water loss compensation mechanisms lay the foundation for future blood pressure increase. Vascular inflammation as key marker for cardiovascular comorbidity appears already at early stages of psoriasis showing that psoriasis patients must be considered as cardiovascular high-risk patients from the very early beginning of the disease on. Previously accepted by JID for publication.

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