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5TNF-alpha and IL-1 beta Neutralization Ameliorates Angiotensin II-Induced Cardiac Damage in Male Mice
Alternative TitleEndocrinology
Wang, Yueli1; Li, Yulin1; Wu, Yina1; Jia, Lixin1; Wang, Jijing1; Xie, Bo2; Hui, Mizhou2; Du, Jie1
2014-07-01
Source PublicationENDOCRINOLOGY
ISSN0013-7227
Volume155Issue:7Pages:2677-2687
AbstractInflammation is a key event in hypertensive organ damage, and TNF-alpha and IL-1 beta are elevated in hypertension. In this study, we evaluated the effects of TNF-alpha and IL-1 beta elevation on hypertensive cardiac damage by treatment with a bifunctional inflammatory inhibitor, TNF receptor 2-fragment crystalization-IL-1 receptor antagonist (TFI), which can neutralize these 2 cytokines simultaneously. A mouse hypertension model of angiotensin II (Ang II) infusion (1500 ng/kg.min for 7 d) was induced in wild-type mice. TNF-alpha and IL-1 beta were inhibited by TFI administration (5 mg/kg, every other day), the effects of inhibition on cardiac damage were examined, and its mechanism on inflammatory infiltration was further studied in vivo and in vitro. Ang II infusion induced cardiac injury, including increased macrophage infiltration, expression of inflammatory cytokines (IL-12, IL-6, etc), and cardiac fibrosis, such as elevated alpha-smooth muscle actin, collagen I, and TGF-beta expression. Importantly, the Ang II-induced cardiac injury was suppressed by TFI treatment. Moreover, TFI reduced the expression of adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) and monocyte chemotactic protein-1 expression in Ang II-treated hearts. Additionally, blockade of TNF-alpha and IL-1 beta by TFI reduced monocyte adherence to endothelia cell and macrophage migration. This study demonstrates that blocking TNF-alpha and IL-1 beta by TFI prevents cardiac damage in response to Ang II, and targeting these 2 cytokines simultaneously might be a novel tool to treat hypertensive heart injury.; Inflammation is a key event in hypertensive organ damage, and TNF-alpha and IL-1 beta are elevated in hypertension. In this study, we evaluated the effects of TNF-alpha and IL-1 beta elevation on hypertensive cardiac damage by treatment with a bifunctional inflammatory inhibitor, TNF receptor 2-fragment crystalization-IL-1 receptor antagonist (TFI), which can neutralize these 2 cytokines simultaneously. A mouse hypertension model of angiotensin II (Ang II) infusion (1500 ng/kg.min for 7 d) was induced in wild-type mice. TNF-alpha and IL-1 beta were inhibited by TFI administration (5 mg/kg, every other day), the effects of inhibition on cardiac damage were examined, and its mechanism on inflammatory infiltration was further studied in vivo and in vitro. Ang II infusion induced cardiac injury, including increased macrophage infiltration, expression of inflammatory cytokines (IL-12, IL-6, etc), and cardiac fibrosis, such as elevated alpha-smooth muscle actin, collagen I, and TGF-beta expression. Importantly, the Ang II-induced cardiac injury was suppressed by TFI treatment. Moreover, TFI reduced the expression of adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) and monocyte chemotactic protein-1 expression in Ang II-treated hearts. Additionally, blockade of TNF-alpha and IL-1 beta by TFI reduced monocyte adherence to endothelia cell and macrophage migration. This study demonstrates that blocking TNF-alpha and IL-1 beta by TFI prevents cardiac damage in response to Ang II, and targeting these 2 cytokines simultaneously might be a novel tool to treat hypertensive heart injury.
KeywordTumor-necrosis-factor Corneal Epithelial-cells Target Organ Damage Factor-alpha Tnf-alpha Heart-failure Endothelial-cells Monocyte Adhesion Hypertension Role Il-1 Pathways
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1210/en.2013-2065
URL查看原文
Indexed BySCI
Language英语
WOS KeywordTUMOR-NECROSIS-FACTOR ; CORNEAL EPITHELIAL-CELLS ; TARGET ORGAN DAMAGE ; FACTOR-ALPHA ; TNF-ALPHA ; HEART-FAILURE ; ENDOTHELIAL-CELLS ; MONOCYTE ADHESION ; HYPERTENSION ROLE ; IL-1 PATHWAYS
WOS Research AreaEndocrinology & Metabolism
WOS SubjectEndocrinology & Metabolism
WOS IDWOS:000342343400034
Citation statistics
Cited Times:22[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Version出版稿
Identifierhttp://ir.ipe.ac.cn/handle/122111/11659
Collection研究所(批量导入)
Affiliation1.Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Key Lab Remodeling Related Cardiovasc Dis,Minist, Beijing 100029, Peoples R China
2.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
Recommended Citation
GB/T 7714
Wang, Yueli,Li, Yulin,Wu, Yina,et al. 5TNF-alpha and IL-1 beta Neutralization Ameliorates Angiotensin II-Induced Cardiac Damage in Male Mice[J]. ENDOCRINOLOGY,2014,155(7):2677-2687.
APA Wang, Yueli.,Li, Yulin.,Wu, Yina.,Jia, Lixin.,Wang, Jijing.,...&Du, Jie.(2014).5TNF-alpha and IL-1 beta Neutralization Ameliorates Angiotensin II-Induced Cardiac Damage in Male Mice.ENDOCRINOLOGY,155(7),2677-2687.
MLA Wang, Yueli,et al."5TNF-alpha and IL-1 beta Neutralization Ameliorates Angiotensin II-Induced Cardiac Damage in Male Mice".ENDOCRINOLOGY 155.7(2014):2677-2687.
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