Tumor Necrosis Factor Alpha Deficiency Improves Endothelial Function and Cardiovascular Injury in Deoxycorticosterone Acetate/Salt-Hypertensive Mice. (28th February 2020)

• Record Type: Journal Article
• Authors: Cai, Ruiping; Hao, Yun; Liu, Yue-Yang; Huang, Lei; Yao, Yang; Zhou, Ming-Sheng
• Other Names: Ye-Na Lee Guest Editor.
• Is Part Of: BioMed research international. Volume 2020(2020)
• Publication Date: 2020-02-28
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2020/3921074
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : It has been shown that the inflammatory cytokine tumor necrosis factor α (TNF α ) plays a role in the development of hypertension and end-stage renal diseases. We hypothesize that TNF α contributes to endothelial dysfunction and cardiac and vascular injury in deoxycorticosterone acetate (DOCA)/salt-hypertensive mice. The wild-type or TNF α -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). TNF α 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 TNF α, interleukin 1 β (IL1 β ), monocyte chemotactic protein 1 (MCP1), and monocyte/macrophage marker F4/80 were significantly increased in the aorta of DOCA-hypertensive mice; TNF α 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. TNF α 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; TNF α deficiency prevented a decrease in eNOS expression and an increase in miR155 expression in DOCA mice. These results support the idea that TNF α significantly contributes to vascular inflammation, vascular dysfunction, and injury in hypertension.