Exacerbated cardiac fibrosis and impaired vascular function following myocardial infarction in a murine model of psoriasis

A. Lehmann (Mainz)¹, M. Aluia (Mainz)², M. Assmann (Mainz)³, S. Khraisat (Mainz)⁴, Q. Luo (Mainz)⁴, F. Moreira (Mainz)⁵, F. Reusswig (Mainz)⁶, J. Ringen (Mainz)¹, V. S. Garlapati (Mainz)⁷, S. Finger (Mainz)², M. Molitor (Mainz)⁷, C. Deppermann (Mainz)⁶, P. Lurz (Mainz)⁴, A. Waisman (Mainz)⁸, P. Wenzel (Darmstadt)⁹, S. Karbach (Mainz)^7
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; ³Centrum für Thrombose und Hämostase (CTH) AG Wenzel Mainz, Deutschland; ⁴Universitätsmedizin der Johannes Gutenberg-Universität Mainz Kardiologie 1, Zentrum für Kardiologie Mainz, Deutschland; ⁵Universitätsmedizin der Johannes Gutenberg-Universität Mainz Center for Thrombosis and Hemostasis Mainz, Deutschland; ⁶Universitätsmedizin Mainz Centrum für Thrombose und Hämostase Mainz, Deutschland; ⁷Universitätsmedizin der Johannes Gutenberg-Universität Mainz Zentrum für Kardiologie Mainz, Deutschland; ⁸Universitätsmedizin Mainz Institut für Molekulare Medizin Mainz, Deutschland; ⁹Klinikum Darmstadt Medizinische Klinik I Darmstadt, Deutschland

The autoimmune disease psoriasis has been known as an independent cardiovascular risk factor. Patients die earlier of cardiovascular diseases and develop for example myocardial infarctions (MI) approximately five years earlier than non-psoriasis patients. Therefore, our aim is to investigate the impact of psoriasis on cardiac function, survival and inflammation after MI in a drug-induced model of psoriasis.
Male C57BL/6J mice were treated with imiquimod (IMQ), a toll like receptor 7/8 agonist and immune activator, vs sham cream for five days to induce psoriasis. Permanent LAD ligation was performed on d6 (PASI: 5-8) and they were sacrificed 8 days after. Transthoracic echocardiography was performed on d7. Histology sections of the hearts were stained with Sirius Red and quantified. Vascular function was evaluated by aortic isometric tension study. Cardiac tissue was investigated by Western Blot analysis and qRT-PCR was conducted on aortic tissue. Flow cytometry analysis was performed on infarcted heart tissue and aortic tissue.
There were no differences in the left ventricular ejection fraction in the IMQ treated mice compared to sham after MI. Sirius Red staining revealed exacerbated collagen and Western Blot analysis showed increased levels of TGF-β1 and α-SMA in the infarcted area of the IMQ treated mice. Aortic relaxation was decreased, inflammatory markers (TNF-α, MCP-1, VCAM-1, IL-6) and ROS/RNS levels were higher in the IMQ treated mice. We didn’t find any significant changes in the infiltration of the myeloid cells in the infarcted area between sham vs. IMQ treatment. Under IMQ treatment alone, the expression of GPIbα, CD61 and GPVI on the platelet surface was upregulated and the platelets showed pre-activation and therefore reacted less to stimuli.
These findings suggest that IMQ treatment leads to exacerbated cardiac fibrosis and impaired aortic function after myocardial infarction, which could explain the worsened outcome psoriasis patients experience following MI. 
Immunoskin SFB Mainz-HD-Tübingen (TRR 156) and the DZHK Excellence Programme (S. Karbach).