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  • Ovid Technologies (Wolters Kluwer Health)  (5)
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  • Ovid Technologies (Wolters Kluwer Health)  (5)
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  • 1
    Online Resource
    Online Resource
    Prostaglandin E2 promotes hepatic bile acid synthesis by an E prostanoid receptor 3‐mediated hepatocyte nuclear receptor 4α/cholesterol 7α‐hydroxylase pathway in mice
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Hepatology Vol. 65, No. 3 ( 2017-03), p. 999-1014
    Details
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 65, No. 3 ( 2017-03), p. 999-1014
    Abstract: Prostaglandin E 2 (PGE 2 ) is an important lipid mediator of inflammation. However, whether and how PGE 2 regulates hepatic cholesterol metabolism remains unknown. We found that expression of the PGE 2 receptor, E prostanoid receptor 3 (EP3) expression is remarkably increased in hepatocytes in response to hyperlipidemic stress. Hepatocyte‐specific deletion of EP3 receptor ( EP3 hep–/– ) results in hypercholesterolemia and augments diet‐induced atherosclerosis in low‐density lipoprotein receptor knockout ( Ldlr –/– ) mice. Cholesterol 7α‐hydroxylase (CYP7A1) is down‐regulated in livers of EP3hep–/–Ldlr−/− mice, leading to suppressed hepatic bile acid (BA) biosynthesis. Mechanistically, hepatic‐EP3 deficiency suppresses CYP7A1 expression by elevating protein kinase A (PKA)‐dependent Ser143 phosphorylation of hepatocyte nuclear receptor 4α (HNF4α). Disruption of the PKA‐HNF4α interaction and BA sequestration rescue impaired BA excretion and ameliorated atherosclerosis in EP3hep–/–Ldlr−/− mice. Conclusion : Our results demonstrated an unexpected role of proinflammatory mediator PGE 2 in improving hepatic cholesterol metabolism through activation of the EP3‐mediated PKA/HNF4α/CYP7A1 pathway, indicating that inhibition of this pathway may be a novel therapeutic strategy for dyslipidemia and atherosclerosis. (H epatology 2017;65:999‐1014)
    Type of Medium: Online Resource
    ISSN: 0270-9139 , 1527-3350
    URL: Article
    DOI: 10.1002/hep.28928
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1472120-X
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Female Sex as a Risk Factor for Ischemic Stroke and Systemic Embolism in Chinese Patients With Atrial Fibrillation: A Report From the China‐AF Study
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Journal of the American Heart Association Vol. 7, No. 19 ( 2018-10-02)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. 19 ( 2018-10-02)
    Abstract: Previous studies have provided conflicting results as to whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation ( AF ). We investigated whether women with AF were at higher risk of ischemic stroke in the China‐AF (China Atrial Fibrillation Registry) Study. Methods and Results A total of 19 515 patients were prospectively enrolled between August 2011 and December 2016 in the China‐ AF Study. After exclusion of patients receiving anticoagulation or ablation therapy, 6239 patients (2574 women) with results from at least 6 months of follow‐up were used for the analysis. Cox proportional hazards models were performed to evaluate whether female sex was an independent risk factor for thromboembolism after multivariate adjustment. The primary outcome was the time to the first occurrence of ischemic stroke or systemic embolism. After a mean follow‐up of 2.81±1.46 years, 152 female patients reached the primary outcome, as compared with 172 male patients. Crude incidence rates of thromboembolism between women and men were of borderline statistical significance (2.08 versus 1.68 per 100 patient‐years, P =0.058). After multivariable analysis, female sex was not independently associated with an increased thromboembolism risk (hazard ratio 1.09, 95% confidence interval 0.86‐1.39). There was no significant difference in thromboembolism risk by sex stratified by age and presence or absence of risk factors ( P for interaction all 〉 0.1). Conclusions Although crude incidence rates of thromboembolism were higher in Chinese female patients with AF compared with male patients, female sex did not emerge as an independent risk factor for thromboembolism on multivariate analysis. Clinical Trial Registration URL : http://www.chictr.org.cn/ . Unique identifier: Chi CTR ‐ OCH ‐13003729.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.118.009391
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2653953-6
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Infection of common marmosets with hepatitis C virus/GB virus-B chimeras
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Hepatology Vol. 59, No. 3 ( 2014-03), p. 789-802
    Details
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 59, No. 3 ( 2014-03), p. 789-802
    Type of Medium: Online Resource
    ISSN: 0270-9139
    URL: Issue
    URL: Article
    DOI: 10.1002/hep.v59.3
    DOI: 10.1002/hep.26750
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1472120-X
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  • 4
    Online Resource
    Online Resource
    Thromboxane Governs the Differentiation of Adipose-Derived Stromal Cells Toward Endothelial Cells In Vitro and In Vivo
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Circulation Research Vol. 118, No. 8 ( 2016-04-15), p. 1194-1207
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. 8 ( 2016-04-15), p. 1194-1207
    Abstract: Autologous adipose-derived stromal cells (ASCs) offer great promise as angiogenic cell therapy for ischemic diseases. Because of their limited self-renewal capacity and pluripotentiality, the therapeutic efficacy of ASCs is still relatively low. Thromboxane has been shown to play an important role in the maintenance of vascular homeostasis. However, little is known about the effects of thromboxane on ASC-mediated angiogenesis. Objective: To explore the role of the thromboxane-prostanoid receptor (TP) in mediating the angiogenic capacity of ASCs in vivo. Methods and Results: ASCs were prepared from mouse epididymal fat pads and induced to differentiate into endothelial cells (ECs) by vascular endothelial growth factor. Cyclooxygenase-2 expression, thromboxane production, and TP expression were upregulated in ASCs on vascular endothelial growth factor treatment. Genetic deletion or pharmacological inhibition of TP in mouse or human ASCs accelerated EC differentiation and increased tube formation in vitro, enhanced angiogenesis in in vivo Matrigel plugs and ischemic mouse hindlimbs. TP deficiency resulted in a significant cellular accumulation of β-catenin by suppression of calpain-mediated degradation in ASCs. Knockdown of β-catenin completely abrogated the enhanced EC differentiation of TP-deficient ASCs, whereas inhibition of calpain reversed the suppressed angiogenic capacity of TP re-expressed ASCs. Moreover, TP was coupled with Gαq to induce calpain-mediated suppression of β-catenin signaling through calcium influx in ASCs. Conclusion: Thromboxane restrained EC differentiation of ASCs through TP-mediated repression of the calpain-dependent β-catenin signaling pathway. These results indicate that TP inhibition could be a promising strategy for therapy utilizing ASCs in the treatment of ischemic diseases.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.115.307853
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467838-X
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  • 5
    Online Resource
    Online Resource
    Abstract WP130: Prevalence and Predictors of Hemorrhagic Foci on Long-Term Follow-Up MRI of Recent Single Subcortical Infarcts
    Ovid Technologies (Wolters Kluwer Health) ; 2024
    In:  Stroke Vol. 55, No. Suppl_1 ( 2024-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. Suppl_1 ( 2024-02)
    Abstract: Background: Hemorrhagic foci surrounding the lacune in the long-term evolution of recent single subcortical infarcts (RSSIs) remains largely unexplored. We aimed to determine the prevalence, characteristics, and predictors of hemorrhagic foci in patients with RSSI. Methods: From a prospective, longitudinal study of RSSIs, we recruited patients who underwent multimodal MRI assessments at baseline and approximately one year after stroke onset. Hemorrhagic foci were identified using susceptibility-weighted imaging (SWI). Results: Among 72 patients with RSSI, nearly half (n = 35, 48.6%) had hemorrhagic foci within the index RSSI lesions on follow-up SWI. RSSIs with hemorrhagic foci formation were associated with a longer time to follow-up imaging (median 484 versus 425 days, P = 0.008) and higher likelihood of being located in the anterior circulation compared to those without hemorrhagic foci (100.0% versus 75.7%, P = 0.001). Hemorrhagic foci were also associated with larger lesion size (P 〈 0.001), higher proportion of cavitation formation (P = 0.042), and poorer functional outcome (P = 0.036). In the subset of RSSIs in the LSA territory, after adjustment for covariates, larger initial lesion volume (OR 1.63, 95% CI 1.06-2.53; P = 0.027) and greater reduction in LSA total length (OR 0.60, 95% CI 0.37-0.97; P = 0.035) were independently associated with hemorrhagic foci formation. Conclusion: Half of RSSI patients developed hemorrhagic foci within the lacunes during follow-up SWI. This hemorrhagic feature might represent hemosiderin deposits from a previously thrombosed perforating artery. The pathophysiologic mechanism and clinical implications remain to be determined.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.55.suppl_1.WP130
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2024
    detail.hit.zdb_id: 1467823-8
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