sirolimus and Mucocutaneous-Lymph-Node-Syndrome

Remodeling of the coronary arteries is a common feature in severe cases of Kawasaki disease (KD). This pathology is driven by the dysregulated proliferation of vascular fibroblasts, which can lead to coronary artery aneurysms, stenosis, and myocardial ischemia. We undertook this study to investigate whether inhibiting fibroblast proliferation might be an effective therapeutic strategy to prevent coronary artery remodeling in KD.. We used a murine model of KD (induced by the injection of the Candida albicans water-soluble complex [CAWS]) and analyzed patient samples to evaluate potential antifibrotic therapies for KD.. We identified the mechanistic target of rapamycin (mTOR) pathway as a potential therapeutic target in KD. The mTOR inhibitor rapamycin potently inhibited cardiac fibroblast proliferation in vitro, and vascular fibroblasts up-regulated mTOR kinase signaling in vivo in the CAWS mouse model of KD. We evaluated the in vivo efficacy of mTOR inhibition and found that the therapeutic administration of rapamycin reduced vascular fibrosis and intimal hyperplasia of the coronary arteries in CAWS-injected mice. Furthermore, the analysis of cardiac tissue from KD fatalities revealed that vascular fibroblasts localizing with inflamed coronary arteries up-regulate mTOR signaling, confirming that the mTOR pathway is active in human KD.. Our findings demonstrate that mTOR signaling contributes to coronary artery remodeling in KD, and that targeting this pathway offers a potential therapeutic strategy to prevent or restrict this pathology in high-risk KD patients.

Topics: Animals; Coronary Artery Disease; Coronary Vessels; Disease Models, Animal; Humans; Mice; Mucocutaneous Lymph Node Syndrome; Sirolimus; TOR Serine-Threonine Kinases

1例主诉为"活动后胸闷、胸痛2 d"的13岁7月龄患儿就诊于安徽医科大学第二附属医院儿科。经病史询问、心脏彩超及冠状动脉造影检查，诊断为川崎病、右侧冠状动脉慢性完全闭塞性病变。成功于局部麻醉下进行经皮腔内冠状血管成形术及冠状动脉内雷帕霉素洗脱支架植入术。.

Topics: Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Humans; Mucocutaneous Lymph Node Syndrome; Sirolimus; Treatment Outcome

We report the case of an acutely ill 3-year-old female, with a previous medical history of Kawasaki disease, who presented to care with an acute myocardial infarction. We describe the coordinated therapies employed by pediatric and adult cardiologists aimed to establish coronary revascularization.

Topics: Angioplasty, Balloon; Anticoagulants; Biomarkers; Cardiac Catheterization; Coronary Aneurysm; Coronary Angiography; Coronary Stenosis; Drug-Eluting Stents; Electrocardiography; Everolimus; Female; Humans; Immunosuppressive Agents; Infant; Mucocutaneous Lymph Node Syndrome; Myocardial Infarction; Sirolimus

Topics: Child; Coronary Aneurysm; Coronary Stenosis; Coronary Vessels; Female; Humans; Immunosuppressive Agents; Infusion Pumps, Implantable; Mucocutaneous Lymph Node Syndrome; Sirolimus; Stents