Interaction of IL-6 and TNF-α contributes to endothelial dysfunction in type 2 diabetic mouse hearts

PloS One
Jonghae LeeYoonjung Park

Abstract

Inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), are individually considered as important contributors to endothelial dysfunction in obesity and type 2 diabetes (T2D). However, their interactions in coronary arteriole endothelial dysfunction are uncertain. Therefore, this study aimed to determine the effects of TNF-α and IL-6 interactions on coronary endothelial dysfunction in experimental T2D. The studies used wild type (WT), diabetic mice (db/db), db/db null for TNF (dbTNF-/dbTNF-), and db/db mice treated with neutralizing antibody to IL-6 (anti-IL-6). Endothelium-dependent (acetylcholine [ACh], or luminal flow-induced shear stress) and endothelium-independent (sodium nitroprusside [SNP]) vasodilation of isolated and pressurized coronary arterioles were determined. Quantitative PCR, Western blot, and immunofluorescence staining were utilized for mechanistic studies. Relative to WT, arteriolar dilation to both ACh and flow was attenuated in db/db mice and dbTNF-/dbTNF-. Treatment of dbTNF-/dbTNF- and db/db mice with anti-IL-6 improved arteriolar dilation compared to db/db mice. Immunofluorescence staining illustrated localization of IL-6 within the endothelial cells of coronary arteriol...Continue Reading

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Jan 12, 2020·Cardiovascular Research·Oana SoropDirk J Duncker
Aug 23, 2019·International Journal of Molecular Medicine·Wen KangXin Wang
Jul 19, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rafael FrancoGemma Navarro
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May 18, 2021·Circulation Research·Paul M Ridker, Manas Rane
Jul 16, 2021·Frontiers in Immunology·Bruce K PattersonRodrigo A Mora-Rodríguez

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Methods Mentioned

BETA
Protein Assay
PCR
electron paramagnetic resonance
gene knockout

Software Mentioned

Multigauge

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