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Coronary and aortic endothelial function affected by feedback between adiponectin and tumor necrosis factor α in type
Hanrui Zhang1, Yoonjung Park, Cuihua Zhang
1Department of Internal Medicine, University of Missouri, Columbia, MO 65211, USA.
Objective:
To verify that adiponectin and tumor necrosis factor (TNF)-α reciprocally regulate their expression, thereby synergistically affecting both coronary and aortic endothelial dysfunction in type 2 diabetic mice.
Methods And Results:
We examined endothelium-dependent and endothelium-independent vasodilation/vasorelaxation of coronary arterioles and aortas in control mice, diabetic mice (Lepr(db)), and Lepr(db) treated with adiponectin or neutralizing antibody to TNF-α (anti-TNF-α). Endothelium-dependent vasodilation to acetylcholine in both coronary arterioles and aortas was blunted in Lepr(db) compared with control mice. Endothelium-independent vasodilation to sodium nitroprusside was comparable. Adiponectin and anti-TNF-α improved acetylcholine-induced vasodilation of coronary arterioles and aortas in Lepr(db) without affecting dilator response to sodium nitroprusside. Adiponectin protein expression was significantly reduced, and TNF-α protein expression was significantly greater, in coronary arterioles and aortas of Lepr(db) compared with control mice. Immunofluorescence staining results indicate that adiponectin was colocalized with endothelial cells. Anti-TNF-α treatment upregulated adiponectin protein expression in Lepr(db) coronary arterioles and aortas. Adiponectin administration reduced TNF-α protein expression in Lepr(db). Although adiponectin receptor 1 protein expression in coronary arterioles and aortas was similar between control and diabetic mice, adiponectin receptor 2 protein expression was significantly reduced in Lepr(db). Both adiponectin and anti-TNF-α inhibited IκBα phosphorylation and nuclear factor κB protein expression in Lepr(db), suggesting that adiponectin and TNF-α signaling may converge on nuclear factor κB to reciprocally regulate their expression.
Conclusions:
A reciprocal suppression occurs between adiponectin and TNF-α that fundamentally affects the regulation of coronary and aortic endothelial function in type 2 diabetic mice.
Insights
Adiponectin and tumor necrosis factor-alpha (TNF-α) reciprocally regulate each other, impacting blood vessel function in type 2 diabetes. This interaction affects endothelial dysfunction in coronary and aortic vessels.
Area of Science:
- Cardiovascular Biology
- Metabolic Disease Research
- Endocrinology
Background:
- Type 2 diabetes is associated with endothelial dysfunction.
- Adiponectin and TNF-α play critical roles in metabolic and inflammatory processes.
- Their interplay in diabetic cardiovascular complications requires elucidation.
Purpose of the Study:
- To investigate the reciprocal regulation between adiponectin and TNF-α.
- To determine their synergistic effects on coronary and aortic endothelial dysfunction in type 2 diabetic mice.
Main Methods:
- Assessment of vasodilation in coronary arterioles and aortas of control and diabetic mice (Lepr(db)).
- Treatment of diabetic mice with adiponectin or anti-TNF-α antibody.
- Measurement of adiponectin and TNF-α protein expression via immunofluorescence.
- Analysis of signaling pathways including IκBα phosphorylation and nuclear factor κB.
Main Results:
- Diabetic mice exhibited blunted endothelium-dependent vasodilation and altered adiponectin/TNF-α expression.
- Adiponectin and anti-TNF-α treatments improved vasodilation and normalized protein expression.
- Both treatments inhibited IκBα phosphorylation and nuclear factor κB activation.
- Adiponectin receptor 2 expression was reduced in diabetic mice.
Conclusions:
- A reciprocal suppression exists between adiponectin and TNF-α in type 2 diabetic mice.
- This interaction fundamentally impacts the regulation of coronary and aortic endothelial function.
- Targeting this pathway may offer therapeutic potential for diabetic cardiovascular complications.
