Mami Wael, Znaidi-Marzouki Soumaya, Doghri Raoudha, Ben Ahmed Melika, Znaidi Sadri, Messadi Erij
Plateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomolécules, Venins et Applications Théranostiques (LR20IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia.
Laboratoire de Transmission, Contrôle et Immunobiologie des Infections (LR16IPT02), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia.
Biomedicines. 2023 Nov 1;11(11):2945. doi: 10.3390/biomedicines11112945.
(1) Background: Increased risk of myocardial infarction (MI) has been linked to several inflammatory conditions, including inflammatory bowel disease (IBD). However, the relationship between IBD and MI remains unclear. Here, 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. (2) Methods: An IBD model was established by dextran sulfate sodium (DSS) administration in drinking water, alone or with oral () 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. (3) Results: 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. inoculation tended to worsen DSS-induced systemic inflammation and IR injury, an observation which is not statistically significant. (4) Conclusions: This is the first proof-of-concept study demonstrating the impact of IBD on MI severity and suggesting mechanistic aspects involved in the IBD-MI connection. Our findings could pave the way for MI therapeutic approaches based on identified IBD-induced inflammatory mediators.
(1) 背景:心肌梗死(MI)风险增加与多种炎症性疾病相关,包括炎症性肠病(IBD)。然而,IBD与MI之间的关系仍不明确。在此,我们构建了一种将IBD和MI相结合的原创小鼠模型,以确定IBD对MI严重程度的影响以及这两种疾病之间的联系。(2) 方法:通过在饮用水中给予葡聚糖硫酸钠(DSS)单独或联合口服()灌胃建立IBD模型。通过临床/组织学评分以及肠道/全身炎症生物标志物测量来评估IBD严重程度。对小鼠进行心肌缺血再灌注(IR),通过量化梗死面积(IS)和血清心肌肌钙蛋白I(cTnI)水平来评估MI严重程度。(3) 结果:IBD小鼠粪便脂质运载蛋白2(Lcn2)和白细胞介素-6水平升高。与对照组相比,DSS小鼠的IS增加了近两倍,血清cTnI水平与IS密切相关。接种倾向于加重DSS诱导的全身炎症和IR损伤,这一观察结果无统计学意义。(4) 结论:这是第一项概念验证研究,证明了IBD对MI严重程度的影响,并提示了IBD与MI关联中涉及的机制方面。我们的发现可能为基于已确定的IBD诱导的炎症介质的MI治疗方法铺平道路。