Question: The autoimmune skin disease psoriasis has been acknowledged as an independent cardiovascular risk factor. Patients develop myocardial infarctions around five years earlier than non-psoriasis patients and die more often of cardiac reasons. Our aim is to investigate the outcome of myocardial infarction with focus on the cardiac function, survival and the inflammation in murine psoriasis.
Methods: Male 8-10 weeks C57BL/6J mice were treated with Imiquimod (IMQ, TLR 7 and 8 agonist) vs sham cream on the dorsal skin and the ears to induce an acute psoriasis-like skin inflammation. After five days of treatment, they were subjected to total LAD ligation (PASI score: 5-8) and sacrificed 8 days afterwards. Transthoracic echocardiography was performed one day before sacrifice. Histology sections of the heart were stained with Sirius Red and quantified. Western Blot was performed on infarcted and remote heart tissue. The aortic tissue was analysed by isometric tension study and qRT-PCR. Aortic rings were stained with dihydroethidium to detect reactive oxygen species. Platelet activity and glycoprotein expression was checked in IMQ treated mice before MI and platelet neutrophil complexes (PNC) were measured 3 days after MI.
Results: No differences in the left ventricular ejection fraction could be found in the IMQ treated mice compared to the sham treated ones after MI. Under IMQ treatment, platelets showed a higher expression of GPIbα, CD61 and GPVI and reacted less to stimuli like the collagen related peptide which could give hint for a situation of exhaustion under chronic inflammation. However, Sirius Red staining revealed an increased collagen content in the infarcted hearts of the IMQ treated mice. Western Blot analysis showed elevated levels of TGF-β1 and α-SMA in the infarcted area of the IMQ treated mice which could give hint for a pro-fibrotic pathway. In parallel, aortic relaxation was reduced and inflammatory markers such as TNF-α, MCP-1, VCAM-1 and IL-6 were increased in the IMQ treated mice. We also found higher levels of ROS/RNS in the aortas of the IMQ treated compared to the sham treated mice.
Conclusion: Our results indicate that IMQ treatment leads to increased cardiac fibrosis and reduced aortic function after myocardial infarction, which could explain the worsened outcome observed in psoriasis patients following myocardial infarction.
Immunoskin SFB Mainz-HD-Tübingen (TRR 156) and the DZHK Excellence Programme (S. Karbach).
