The involvement of the vasa vasorum in the development of vasculitis in animal model of Kawasaki disease

Abstract

BackgroundKawasaki Disease (KD) involves a diffuse and systemic vasculitis of unknown etiology that mainly affects infants and children. Although a considerable number of analyses of the clinical, histopathological and molecular biological details underlying the mechanism responsible for the development of coronary arterial lesions, it is still poorly understood.The purpose of this study was to analyze the state of angiogenesis, vasculogenesis and the distribution of blood vessels using an animal model of KD like vasculitis. We investigated the involvement of the vasa vasorum from the adventitia in the vascular involvement and the development of the disease state by performing sequential histopathology, scanning electron microscopy (SEM) and micro computed tomography (CT) studies using a murine model of vasculitis induced by the Candida albicans water-soluble fraction (CAWS).MethodsTo prepare the animal model of KD like vasculitis, CAWS was intraperitoneally injected into C57BL/6N mice for five consecutive days as reported by Ohno et al. We observed the changes of the vasa vasorum at the aorta and the orifices of the coronary arteries by SEM and micro CT, and also compared the neovascularization at the media and adventitia of the aorta by an immunohistochemical analysis.ResultsAs previously reported, obvious inflammation was detected two weeks after the injection of CAWS, and also intimal thickening was observed three weeks after the injection. We found that the vasa vasorum in the adventitia of the aorta was increased in the model mice. The vasa vasorum started increasing one week after the injection of CAWS, before any obvious vasculitis was microscopically detected.ConclusionThe present results indicate that the vasculitis in Kawasaki disease starts as a disorder of the vasa vasorum.

Identifying Differences in Risk Factors for Depression and Anxiety in Pediatric Chronic Disease: A Matched Cross-Sectional Study of Youth with Lupus/Mixed Connective Tissue Disease and Their Peers with Diabetes

“…Several studies indicate that depression and anxiety rates are high in youth from many chronic disease groups, 6, 10, 12 but little is known about the differences between these groups. As a first step in looking beyond the known associations of depression and anxiety with adolescent age, female sex and the presence of chronic disease, we utilized a matched cross-sectional analysis to compare risk factors for depression and anxiety in two pediatric chronic disease cohorts of similar age group and sex.…”

“…Although primary care providers have been identified as mediators for mental health intervention in youth in general, 45 those with chronic disease like SLE/MCTD typically see their subspecialty providers more often 6 and may benefit from intervention at subspecialty care sites. 6 Recent literature indicating successful implementation of depression screening in youth with T1D at outpatient diabetes clinic visits 46 is encouraging for feasibility of subspecialty-based intervention, potentially increasing mental health treatment rates, reducing disparities in care and improving outcomes. Further investigation of effective strategies for mental health symptom recognition and intervention for youth with chronic disease is needed.…”

“…1 In contrast to the prevalence of depression in 11%, suicidal ideation in 6% and anxiety in 8% of the United States general adolescent population, 2, 3 these disorders occur in up to 60%, 20% and 35%, respectively, of youth with SLE/MCTD. 4-6 While the cause of this remains unclear, potential reasons include social, cultural and genetic factors in the predominantly non-white SLE/MCTD population, the psychological burden of chronic disease, effects of steroid treatment and CNS inflammation, which is recognized as a cause of mood and anxiety disorders in SLE. 7 Among youth with SLE/MCTD and other chronic disease, there is little known about differences in depression and anxiety etiology between disease groups, and elucidating the contributing factors may guide more effective recognition and treatment of these conditions in these patients.…”

Inflammatory and Immune Responses in the Arterial Media

“…Even though lymphatic channels are not found in the media of normal and arteriosclerotic coronary arteries, it does not exclude soluble antigen or even rare antigen-presenting cells from extravasation into the adventitia where they may collect into perivascular lymphatic vessels. 75 It has not been determined whether direct introduction of foreign antigens into the arterial media can immunize the recipient, although antigen expression in other avascular immunoprivileged tissues can succeed or fail to activate immunity depending on the experimental conditions. 76,77 A reasonable assumption for medial immunoprivilege is an elastin barrier to cellular traffic.…”

Recent updates on echocardiography and ultrasound for Kawasaki disease: beyond the coronary artery

“…In fact, Takahashi et al demonstrated that the inflammatory changes in the adventitia occur prior to the changes in the intima in various animal models of KD vasculitis (45). Furthermore, Hamaoka-Okamoto et al revealed that the proliferation of adventitial VV was accompanied by an increase in the inflammation confirmed by a scanning electron microscope (SEM) in a murine model of KD vasculitis (46). Additionally, in specimens of coronary arteries from KD patients with CAAs, Suzuki et al showed that the overexpression of GFs was observed in the microvessels of the thick intima and there was an expanded VV network in the adventitia (32).…”