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Published on: June 10, 2015
Tumor Necrosis Factor Alpha Deficiency Improves Endothelial Function and Cardiovascular Injury in Deoxycorticosterone
Ruiping Cai1, Yun Hao2, Yue-Yang Liu1
1Department of Physiology, Shenyang Medical College, Shenyang 110034, China.
Insights
Tumor necrosis factor-alpha (TNFα) drives hypertension-related vascular inflammation and dysfunction. Targeting TNFα in mice reduced inflammation, oxidative stress, and improved blood vessel function, suggesting a therapeutic role.
Area of Science:
- Cardiovascular Biology
- Inflammation and Immunology
- Renal Physiology
Background:
- Tumor necrosis factor-alpha (TNFα) is implicated in hypertension and renal disease.
- Endothelial dysfunction, cardiac, and vascular injury are key complications of hypertension.
Purpose of the Study:
- To investigate the role of TNFα in deoxycorticosterone acetate (DOCA)/salt-induced hypertension.
- To determine if TNFα contributes to endothelial dysfunction and organ injury in a mouse model.
Main Methods:
- Utilized wild-type and TNFα-deficient mice subjected to DOCA/salt treatment.
- Assessed systolic blood pressure, cardiac/vascular hypertrophy, and endothelium-dependent relaxation.
- Analyzed inflammatory gene expression, oxidative stress markers, fibrotic factors, and eNOS/miR155 levels.
Main Results:
- DOCA mice exhibited hypertension, hypertrophy, and impaired endothelial relaxation.
- TNFα deficiency attenuated these effects, improving endothelial function and reducing hypertrophy.
- TNFα deficiency decreased inflammatory gene expression, oxidative stress, and fibrosis in DOCA mice.
- TNFα deficiency prevented eNOS reduction and miR155 upregulation in DOCA mice.
Conclusions:
- TNFα significantly contributes to vascular inflammation, dysfunction, and injury in hypertension.
- Targeting TNFα may offer a therapeutic strategy for managing hypertensive complications.
- The study highlights TNFα's role in mediating oxidative stress and fibrosis in hypertension.
Abstract:
It has been shown that the inflammatory cytokine tumor necrosis factor α (TNFα) plays a role in the development of hypertension and end-stage renal diseases. We hypothesize that TNFα contributes to endothelial dysfunction and cardiac and vascular injury in deoxycorticosterone acetate (DOCA)/salt-hypertensive mice. The wild-type or TNFα-deficient mice were uninephrectomized and implanted with DOCA pellet treatment for 5 weeks; the mice were given either tap water or 1% NaCl drinking water. DOCA mice developed hypertension (systolic blood pressure (SBP): 167 ± 5 vs. 110 ± 4 mmHg in control group, p < 0.05), cardiac and vascular hypertrophy, and the impairment of endothelium-dependent relaxation to acetylcholine (EDR). TNFα deficiency improved EDR and lowered cardiac and vascular hypertrophy with a mild reduction in SBP (152 ± 4 vs. 167 ± 5 mmHg in DOCA group, p < 0.05) in DOCA mice. The mRNA expressions of the inflammatory cytokines, including TNFα, interleukin 1β (IL1β), monocyte chemotactic protein 1 (MCP1), and monocyte/macrophage marker F4/80 were significantly increased in the aorta of DOCA-hypertensive mice; TNFα deficiency reduced these inflammatory gene expressions. DOCA-hypertensive mice also exhibited an increase in the vascular oxidative fluorescence intensities, the protein expressions of gp91phox and p22phox, and the fibrotic factors transforming growth factor β and fibronectin. TNFα deficiency reduced oxidative stress and fibrotic protein expressions. The DOCA mice also showed a decrease in the protein expression of eNOS associated with increased miR155 expression; TNFα deficiency prevented a decrease in eNOS expression and an increase in miR155 expression in DOCA mice. These results support the idea that TNFα significantly contributes to vascular inflammation, vascular dysfunction, and injury in hypertension.
