Clin Res Cardiol (2025). DOI 10.1007/s00392-025-02737-x
1Universitätsmedizin der Johannes Gutenberg-Universität Mainz Centrum für Thrombose und Hämostase Mainz, Deutschland; 2Universitätsmedizin der Johannes Gutenberg-Universität Mainz Center of Thrombosis and Hemostasis Mainz, Deutschland; 3University Hospital Heidelberg Department of Dermatology Heidelberg, Deutschland; 4Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Deutschland; 5Universitätsmedizin Mainz Institut für Molekulare Medizin Mainz, Deutschland; 6Klinikum Darmstadt Medizinische Klinik I Darmstadt, Deutschland; 7Universitätsmedizin der Johannes Gutenberg-Universität Mainz Zentrum für Kardiologie Mainz, Deutschland
Question: The Interleukin-17A mediated chronic, auto-inflammatory disease psoriasis is associated with cardiovascular disease. Psoriasis itself has meanwhile been accepted as new cardiovascular risk-factor on its own. However, the majority of psoriasis patients suffer from classical CVRF on top and are not aware of the risk they are facing. Our straight-forward aim was to analyse the impact of high-fat diet on dermal, systemic and vascular inflammation in murine Interleukin-17A driven psoriasis-like skin disease.
Methods: In order to simulate the effects of fatty nutrition, 4 to 6 weeks old hetero- and homozygous CD11cCre-positive-IL-17Aind psoriatic mice (IL-17A overexpression in dendritic cells as model of moderate psoriasis) were fed with Western Diet vs Regular Diet (RD) over 16 weeks. Baseline homozygous CD11c+IL-17Aind/ind psoriatic mice show a more severe skin phenotype with an earlier onset compared to the heterozygous CD11c+IL-17Aind/+ psoriatic mice as previously shown. Skin analysis was performed by Psoriasis Area and Severity Index PASI score during the diet and afterwards, mice were euthanized and vascular function, oxidative stress formation and vascular inflammation were analysed by vascular relaxation measurement, chemiluminescence, flow cytometry and immunohistochemistry. Besides, liver, spleen, skin as well as the epididymal and inguinal adipose tissue were examined by flow cytometry. On top, inflammatory markers were determined by ELISA and q-PCR.
Results: Especially the homozygous psoriatic mice fed with Western Diet showed an exacerbating dermal inflammation with increased neutrophil infiltration in the skin compared to the homozygous psoriatic mice on regular diet and compared to control mice on Western Diet. Even more importantly, we found a reduced vascular relaxation capacity combined with increased vascular infiltration of myeloid cells and increased systemic production of ROS/RNS. This was associated with increased concentrations of the cytokine IL-17A in the blood in correlation with increasing severity of the psoriasis and hint for increased systemic inflammation. Furthermore, homozygous CD11c+IL-17Aind/ind psoriatic mice tended to have elevated GTP/ALT levels after eight weeks on diet already, giving hint for early liver damage.
Summary: Taken together, high-fat diet on top to the cardiovascular risk factor psoriasis seems to be more than a cardiovascular risk factor on top – but interacts on multiple ways with the local skin inflammation, systemic inflammation and vascular inflammation and function with an aggravating impact. This is something we must be aware of when facing patients with autoimmune diseases associated with cardiovascular disease. Further analysis will follow to pave the way for better treatment options.