https://doi.org/10.1007/s00392-025-02625-4
1Universitätsmedizin der Johannes Gutenberg-Universität Mainz Center of Thrombosis and Hemostasis Mainz, Deutschland; 2Universitätsmedizin der Johannes Gutenberg-Universität Mainz Centrum für Thrombose und Hämostase Mainz, Deutschland; 3Universitätsmedizin der Johannes Gutenberg-Universität Mainz Zentrum für Kardiologie Mainz, Deutschland; 4Universitätsmedizin der Johannes Gutenberg-Universität Mainz Kardiologie 1, Zentrum für Kardiologie Mainz, Deutschland; 5Universitätsmedizin der Johannes Gutenberg-Universität Mainz Institut für Molekulare Medizin Mainz, Deutschland
Background: The Interleukin-17A driven autoimmune skin disease psoriasis is recognized as an independent cardiovascular risk factor. Psoriasis patients develop myocardial infarctions (MI) around five years earlier than non-psoriasis patients. The exact mechanisms are still unclear.
Objective: Our project focuses on the impact of the autoimmune skin disease on cardiac function, survival and inflammation following myocardial infarction in murine psoriasis.
Methods: Male C57BL/6J mice (8-10 weeks old) were treated daily with imiquimod (IMQ, TLR 7 and 8 agonist) vs sham cream on the dorsal skin and on the ears for five days to evoke the classically drug induced murine model of psoriasis like skin disease.
Mice were subjected to permanent LAD ligation (PASI score: 5-8) and sacrificed 3 and 8 days afterwards, respectively. Transthoracic echocardiography was performed on d2 and d7, respectively. The cell composition of the heart was determined via flow cytometry. Histology sections of the hearts were stained with Masson-Goldner-Trichrome and Sirius Red and quantified to measure the percentage of collagen in the hearts. Endothelial function was analysed by isometric tension study testing aortic relaxation in response to acetylcholine. The infarcted and the remote heart area was investigated by Western Blot analysis and qRT-PCR was performed on aortic tissue.
Results: Three days after LAD ligation, there was no significant difference in the number of Ly6C+/Ly6G+ neutrophils and Ly6C+/Ly6G- monocytes in the hearts of IMQ- and sham-treated mice. Eight days after LAD ligation, we found lower numbers of cardiac neutrophils (Ly6C+/Ly6G+) and higher levels of cardiac monocytes (Ly6C+/Ly6G-) in the hearts of the IMQ-treated mice. Of note, there was no difference in the ejection fraction neither three nor eight days after LAD ligation in the IMQ-treated mice compared to LAD ligated control mice. However, we found a higher percentage of collagen I and III formation in the hearts after LAD ligation and higher levels of TGFβ in the infarcted area of the psoriatic mice. Besides, aortic endothelial dysfunction was significantly more pronounced in LAD ligated IMQ-treated mice compared to LAD ligated control mice. Three days after MI we already found higher levels of VEGFA in the aorta of the IMQ treated mice. Eight days after MI induction, the expression of TNFα, MCP-1, VCAM-1 and CCR2 was also found to be elevated in the aortas of the psoriatic mice.
Conclusion: IMQ treatment did not lead to differences in the left ventricular ejection fraction but evoked increased cardiac fibrosis formation as well as worsened endothelial dysfunction in murine psoriasis compared to non-psoriatic controls after LAD ligation.