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  • 1
    In: Cardiovascular Research, Oxford University Press (OUP), Vol. 117, No. 1 ( 2021-01-01), p. 96-108
    Abstract: Coronary arteritis is a life-threatening complication that may arise in the acute stage of Kawasaki disease (KD), the leading cause of systemic vasculitis in childhood. Various microorganisms and molecular pathogens have been reported to cause KD. However, little is known about the key molecules that contribute to the development of coronary arteritis in KD. Methods and results To identify causative molecules for coronary arteritis in KD, we prospectively recruited 105 patients with KD and 65 disease controls in four different parts of Japan from 2015 to 2018. During this period, we conducted lipidomics analyses of their sera using liquid chromatography–mass spectrometry (LC-MS). The comprehensive LC-MS system detected a total of 27 776 molecules harbouring the unique retention time and m/z values. In the first cohort of 57 KD patients, we found that a fraction of these molecules showed enrichment patterns that varied with the sampling region and season. Among them, 28 molecules were recurrently identified in KD patients but not in controls. The second and third cohorts of 48 more patients with KD revealed that these molecules were correlated with inflammatory markers (leucocyte counts and C-reactive proteins) in the acute stage. Notably, two of these molecules (m/z values: 822.55 and 834.59) were significantly associated with the development of coronary arteritis in the acute stage of KD. Their fragmentation patterns in the tandem MS/MS analysis were consistent with those of oxidized phosphatidylcholines (PCs). Further LC-MS/MS analysis supported the concept that reactive oxygen species caused the non-selective oxidization of PCs in KD patients. In addition, the concentrations of LOX-1 ligand containing apolipoprotein B in the plasma of KD patients were significantly higher than in controls. Conclusion These data suggest that inflammatory signals activated by oxidized phospholipids are involved in the pathogenesis of coronary arteritis in KD. Because the present study recruited only Japanese patients, further examinations are required to determine whether oxidized PCs might be useful biomarkers for the development of coronary arteritis in broad populations of KD.
    Type of Medium: Online Resource
    ISSN: 0008-6363 , 1755-3245
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1499917-1
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  • 2
    Online Resource
    Online Resource
    American Physiological Society ; 2020
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 319, No. 5 ( 2020-11-01), p. H938-H947
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 319, No. 5 ( 2020-11-01), p. H938-H947
    Abstract: In patients with heart failure, atrial septal defect (ASD) closure has a risk of inducing life-threatening acute pulmonary edema. The objective of this study was to develop a novel framework for quantitative prediction of hemodynamics after ASD closure. The generalized circulatory equilibrium comprises right and left cardiac output (CO) curves and pulmonary and systemic venous return surfaces. We incorporated ASD into the framework of circulatory equilibrium by representing ASD shunt flow (Q ASD ) by the difference between pulmonary flow (Q P ) and systemic flow (Q S ). To examine the accuracy of prediction, we created ASD in six dogs. Four weeks after ASD creation, we measured left atrial pressure (P LA ), right atrial pressure (P RA ), Q P , and Qs before and after ASD balloon occlusion. We then predicted postocclusion hemodynamics from measured preocclusion hemodynamics. Finally, we numerically simulated hemodynamics under various ASD diameters while changing left and right ventricular function. Predicted postocclusion P LA , P RA , and Q S from preocclusion hemodynamics matched well with those measured [P LA : coefficient of determination ( r 2 ) = 0.96, standard error of estimate (SEE) = 0.89 mmHg, P RA : r 2  = 0.98, SEE = 0.26 mmHg, Q S : r 2  = 0.97, SEE = 5.6 mL·min −1 ·kg −1 ]. A simulation study demonstrated that ASD closure increases the risk of pulmonary edema in patients with impaired left ventricular function and normal right ventricular function, indicating the importance of evaluation for the balance between right and left ventricular function. ASD shunt incorporated into the generalized circulatory equilibrium accurately predicted hemodynamics after ASD closure, which would facilitate safety management of ASD closure. NEW & NOTEWORTHY We developed a framework to predict the impact of atrial septal defect (ASD) closure on hemodynamics by incorporating ASD shunt flow into the framework of circulatory equilibrium. The proposed framework accurately predicted hemodynamics after ASD closure. Patient-specific prediction of hemodynamics may be useful for safety management of ASD closure.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2020
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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