Inflammatory bowel disease increases the severity of myocardial infarction after acute ischemia-reperfusion injury in mice

• Published in: Archives of cardiovascular diseases Vol. 117; no. 6-7; p. S176
• Main Authors: Mami, Wael, Znaidi-Marzouki, Soumaya, Doghri, Raoudha, Ben Ahmed, Melika, Znaidi, Sadri, Messadi, Erij
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.06.2024
• ISSN: 1875-2136; 1875-2128
• DOI: 10.1016/j.acvd.2024.05.031

Emerging evidence has shown that chronic inflammatory disorders, including rheumatic arthritis, systemic lupus erythematosus, and ankylosing spondylitis, are associated with an increased risk of heart disease including myocardial infarction (MI). However, the relationship between inflammatory bowel disease (IBD) and MI remains to be fully elucidated. In this study, we aimed (i) to investigate whether a cause–effect relationship exists between IBD and the severity of MI, (ii) to determine the consequences of an inflammatory intestinal disease condition on the onset/development of MI, and (iii) to assess the underlying mechanisms between the two diseases, using animal experimentation as a relevant approach when clinical hypotheses are discordant among patients. We implemented an original mouse model combining IBD and MI to determine IBD's impact on MI severity and the link between the two diseases. An IBD model was established by dextran sulfate sodium (DSS) administration in drinking water, alone or with oral C. albicans (Ca) gavage. IBD severity was assessed by clinical/histological scores and intestinal/systemic inflammatory biomarker measurement. Mice were subjected to myocardial ischemia-reperfusion (IR), and MI severity was assessed by quantifying infarct size (IS) and serum cardiac troponin I (cTnI) levels, after 3 or 24h of reperfusion, respectively. IBD mice exhibited elevated fecal lipocalin 2 (Lcn2) and IL-6 levels. DSS mice exhibited almost two-fold increase in IS compared to controls, with serum cTnI levels strongly correlated with IS. Ca inoculation tended to worsen DSS-induced systemic inflammation and IR injury, an observation, which is not statistically significant. Our work is the first proof-of-concept study to demonstrate the contribution of IBD to the severity of IR and to experimentally propose mechanistic aspects involved in MI susceptibility in IBD subjects. This could pave the way for preventive treatments against cardiovascular diseases in patients with IBD and provide a therapeutic approach for the treatment of MI in the context of IBD based on identified IBD-induced inflammatory mediators.