https://doi.org/10.1007/s00392-024-02526-y
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:
Psoriasis, an IL-17A mediated autoimmune skin disease, has been acknowledged to be an independent cardiovascular risk factor, with psoriasis patients developing myocardial infarctions (MI) around five years earlier than non-psoriasis patients. Further research on the exact mechanisms is necessary.
Psoriasis, an IL-17A mediated autoimmune skin disease, has been acknowledged to be an independent cardiovascular risk factor, with psoriasis patients developing myocardial infarctions (MI) around five years earlier than non-psoriasis patients. Further research on the exact mechanisms is necessary.
Objective:
Our project aims to investigate the impact of psoriasis on cardiac function, inflammation and survival post-myocardial infarction (post-MI) in acute severe Imiquimod (IMQ; TLR 7/8 ligand) induced psoriasis-like skin disease.
Methods:
Male C57BL/6J mice (8-9 weeks old) were treated daily on the dorsal skin and ears with IMQ or sham cream along standard protocol over five days. Platelet reactivity was measured on day 5. Both groups were then subjected to total LAD ligation (PASI score: 5-8). None-invasive blood pressure measurements were performed before and after the MI operation. Transthoracic echocardiography was performed 3 days after MI induction. Afterwards, mice were sacrificed, platelet neutrophil complexes were measured and aortic relaxation was analysed. The infarcted and the remote heart area was analysed by Western Blot and q-RT-PCR was performed on aortic tissue.
Results:
We found no differences in infarct size in IMQ-treated mice compared to sham-treated mice under MI. Blood pressure was not altered neither. Expression of P-Selectin on platelets indicated that the platelets in the IMQ treated mice were preactivated compared to sham treated mice – and less reactive upon stimulation which might give hint to an exhaustion effect. In parallel, platelet neutrophil complexes were reduced in IMQ induced psoriasis. Aortic relaxation was reduced in murine psoriasis post-MI – and in line MCP-1, TNF-alpha, VCMA-1 and CCR-1 were increased by trend in the aortas of these mice.
Conclusion:
We found no differences in infarct size in IMQ treated mice post-MI and hint for pre-activated platelets with an “exhaustion” effect. However, vascular function was significantly reduced post-MI in IMQ treated mice giving hint for vascular disease development in psoriatic mice post-MI.
Funding: Immunoskin SFB Mainz-HD-Tübingen and the DZHK Excellence Programme.