Difference Between Persistent Aneurysm, Regressed Aneurysm, and Coronary Dilation in Kawasaki Disease: An Optical Coherence Tomography Study

Dionne, Audrey; Ibrahim, Ragui; Gebhard, Cathérine; Benovoy, Mitchel; Lèye, Mohamed; Déry, Johanne; Lapierre, Chantale; Girard, Patrice; Fournier, Anne; Dahdah, Nagib

doi:10.1016/j.cjca.2018.05.021

Cited by 26 publications

(27 citation statements)

References 38 publications

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“…32,33 Neovascularization, which is characterized by abnormal endothelial cell proliferation/migration and formation of new microvessels, has been previously implicated in the vascular remodeling process, occurring during the aneurysmal pathogenesis. 34 Indeed, in this study, we have shown that the density of CD31+ microvessels was higher in adventitia and media of human aortic aneurysms when compared with nonaneurysmal aortas. The process of neovascularization requires active participation of MMPs, which degrade the basement membrane and structural matrix of vascular wall, to allow for the proliferation/migration of endothelial cells.…”

Section: Discussionmentioning

confidence: 52%

CD248+CD8+ T lymphocytes suppress pathological vascular remodeling in human thoracic aortic aneurysms

Wu²,

Wang

et al. 2020

Exp Biol Med (Maywood)

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Aortic aneurysms are characterized by vascular inflammation, neovascularization, and extracellular matrix destruction of the aortic wall. Although experimental studies indicate a potential role of CD248 in microvessel remodeling, the functions of CD248 in human vascular pathologies remain unexplored. Here we aimed to study how CD248 interferes with pathological vascular remodeling of human aortic aneurysms. Immunofluorescent staining showed that CD248 expression was mainly localized in the CD8+ T cells infiltrating in the adventitia and media of aortic walls of patients with ascending thoracic aortic aneurysms. qPCR and immunofluorescent staining analyses revealed increased aortic CD248 expression and infiltrating CD248+CD8+ T cells in aortic aneurysms than in nonaneurysmal aortas. Flow cytometry analysis of human peripheral blood further identified a fraction of circulating CD248+ cells which was confined in the CD8+ T-cell compartment. The increased infiltrating of CD248+CD8+ T cells was coincident with reduced circulating CD248+CD8+ T cells in patients with ascending TAA when compared with patients with coronary artery diseases and healthy donors. The CD248+CD8+ T cells were characterized by upregulated IL-10 and downregulated IL-1β/INF-γ expression when compared with CD248-CD8+ T cells. Moreover, when co-cultured with human aortic endothelial cells, the CD248+CD8+ T cells not only downregulated endothelial expression of ICAM1/VCAM1 and MMP2/3 but also suppressed endothelial migration. This study shows that CD248 reduces pathological vascular remodeling via anti-inflammatory CD248+CD8+ T cells, revealing a CD248-mediated cellular mechanism against human aortic aneurysms. Impact statement In spite of recent evidence indicating that CD248 is linked to microvasculature remodeling, immune response, and MMP activity, the functions of CD248 in human TAA remain unexplored. In this work, by analyzing cellular components of in situ as well as of blood circulation of human TAA, we have identified a novel T cell subset, the CD248+CD8+ T cells, which exhibits anti-inflammatory properties, and that we have also provided the first evidence that these cells not only suppress endothelial expression of ICAM1/VCAM1 and MMP2/3, but also inhibit endothelial migration, thus uncovering a CD248-mediated cellular mechanism against pathological vascular remodeling in human aortic aneurysms.

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Section: Discussionmentioning

confidence: 52%

CD248+CD8+ T lymphocytes suppress pathological vascular remodeling in human thoracic aortic aneurysms

Wu²,

Wang

et al. 2020

Exp Biol Med (Maywood)

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“…Comparison of rigid and deformable wall simulation results, for this patient cohort, showed that despite the differences in local WSS, TAWSS sensitivity to changes in coronary arteries Young's modulus and thickness is small, and trends are conserved between rigid and deformable simulations. Nevertheless, additional information regarding patient-specific wall structure and composition, as recently reported using optical coherence tomography [44,45], could improve local assessment of aneurysm wall stress and strain. We did not have evidence of abnormal perfusion as a result of KD for any of the patients in this cohort, so normal myocardial perfusion was considered for all patients.…”

Section: Discussionmentioning

confidence: 97%

Hemodynamic variables in aneurysms are associated with thrombotic risk in children with Kawasaki disease

Gutiérrez

Mathew

McCrindle

et al. 2019

International Journal of Cardiology

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Background: Thrombosis is a major adverse outcome associated with coronary artery aneurysms (CAAs) resulting from Kawasaki disease (KD). Clinical guidelines recommend initiation of anticoagulation therapy with maximum CAA diameter (D max) ≥8 mm or Z-score ≥ 10. Here, we investigate the role of aneurysm hemodynamics as a superior method for thrombotic risk stratification in KD patients. Methods and results: We retrospectively studied ten KD patients with CAAs, including five patients who developed thrombosis. We constructed patient-specific anatomic models from cardiac magnetic resonance images and performed computational hemodynamic simulations using SimVascular. Our simulations incorporated pulsatile flow, deformable arterial walls and boundary conditions automatically tuned to match patient-specific arterial pressure and cardiac output. From simulation results, we derived local hemodynamic variables including time-averaged wall shear stress (TAWSS), low wall shear stress exposure, and oscillatory shear index (OSI). Local TAWSS was significantly lower in CAAs that developed thrombosis (1.2 ± 0.94 vs. 7.28 ± 9.77 dynes/ cm 2 , p = 0.006) and the fraction of CAA surface area exposed to low wall shear stress was larger (0.69 ± 0.17 vs. 0.25 ± 0.26%, p = 0.005). Similarly, longer residence times were obtained in branches where thrombosis was confirmed (9.07 ± 6.26 vs. 2.05 ± 2.91 cycles, p = 0.004). No significant differences were found for OSI or anatomical measurements such us D max and Z-score. Assessment of thrombotic risk according to hemodynamic variables had higher sensitivity and specificity compared to standard clinical metrics (D max , Z-score). Conclusions: Hemodynamic variables can be obtained non-invasively via simulation and may provide improved thrombotic risk stratification compared to current diameter-based metrics, facilitating long-term clinical management of KD patients with persistent CAAs.

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“…Dionne et al describe the use of optical coherence tomography to study the underlying pathophysiology of coronary artery involvement, with fibrosis, cellular infiltration, and intimal hyperplasia being ubiquitous findings and calcification, medial necrosis, neovascularization, and thrombus formation strongly associated with the development of aneurysms. 11 Familial hypercholesterolemia (FH) due to mutations in lipid-metabolism proteins is the most common cause of premature atherosclerosis. To be optimally effective, treatment should begin in childhood, around age 10.…”

Section: Focus On Congenital Heart Disease and Pediatric Cardiologymentioning

confidence: 99%

The Canadian Journal of Cardiology: Open and Growing

Nattel

2019

Canadian Journal of Cardiology

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Difference Between Persistent Aneurysm, Regressed Aneurysm, and Coronary Dilation in Kawasaki Disease: An Optical Coherence Tomography Study

Cited by 26 publications

References 38 publications

CD248+CD8+ T lymphocytes suppress pathological vascular remodeling in human thoracic aortic aneurysms

CD248+CD8+ T lymphocytes suppress pathological vascular remodeling in human thoracic aortic aneurysms

Hemodynamic variables in aneurysms are associated with thrombotic risk in children with Kawasaki disease

The Canadian Journal of Cardiology: Open and Growing

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