PDF(Pubmed)
Abstract：
UNASSIGNED: Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD.
UNASSIGNED: We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram.
UNASSIGNED: CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages.
UNASSIGNED: Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.
UNASSIGNED: We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram.
UNASSIGNED: CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages.
UNASSIGNED: Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.
摘要：
■川崎病（KD），急性发热性疾病和全身性血管炎,是工业化国家儿童获得性心脏病的主要原因。KD导致受影响儿童的冠状动脉瘤（CAA）的发展，这种情况可能会在疾病的急性期后持续数月甚至数年。对于表征KD的长期并发症的免疫和病理机制存在未满足的需要。
■我们在超过4个月的KD样血管炎的干酪乳杆菌细胞壁提取物（LCWE）小鼠模型中检查了心血管并发症。长期免疫，病态,和功能变化发生在心血管病变的特点是组织学检查，流式细胞仪分析,心血管组织免疫荧光染色，和经胸超声心动图.
■在LCWE注射和急性血管炎开始后长达16周检测到CAA和腹主动脉扩张。我们观察到循环免疫细胞谱组成的变化，例如疾病急性期单核细胞频率增加和中性粒细胞计数增加。我们确定循环中性粒细胞和炎性单核细胞计数与LCWE注射后早期心血管病变的严重程度之间呈正相关。LCWE诱导的KD样血管炎与心肌炎和心肌功能障碍有关，以射血分数减少和左心室重构为特征，随着时间的推移而恶化。我们在疾病早期观察到发炎的心脏组织内广泛的纤维化，在后期观察到心肌纤维化。
■我们的发现表明，急性期循环中性粒细胞计数增加是LCWE注射小鼠心血管炎症严重程度的可靠预测指标。此外，由主动脉根部和冠状动脉的炎症细胞浸润引起的长期心脏并发症，心肌功能障碍,和心肌纤维化持续很长一段时间，并且在LCWE注射后16周内仍可检测到。
■我们在超过4个月的KD样血管炎的干酪乳杆菌细胞壁提取物（LCWE）小鼠模型中检查了心血管并发症。长期免疫，病态,和功能变化发生在心血管病变的特点是组织学检查，流式细胞仪分析,心血管组织免疫荧光染色，和经胸超声心动图.
■在LCWE注射和急性血管炎开始后长达16周检测到CAA和腹主动脉扩张。我们观察到循环免疫细胞谱组成的变化，例如疾病急性期单核细胞频率增加和中性粒细胞计数增加。我们确定循环中性粒细胞和炎性单核细胞计数与LCWE注射后早期心血管病变的严重程度之间呈正相关。LCWE诱导的KD样血管炎与心肌炎和心肌功能障碍有关，以射血分数减少和左心室重构为特征，随着时间的推移而恶化。我们在疾病早期观察到发炎的心脏组织内广泛的纤维化，在后期观察到心肌纤维化。
■我们的发现表明，急性期循环中性粒细胞计数增加是LCWE注射小鼠心血管炎症严重程度的可靠预测指标。此外，由主动脉根部和冠状动脉的炎症细胞浸润引起的长期心脏并发症，心肌功能障碍,和心肌纤维化持续很长一段时间，并且在LCWE注射后16周内仍可检测到。
