1. Tumor Necrosis Factor Alpha Deficiency Improves Endothelial Function and Cardiovascular Injury in Deoxycorticosterone Acetate/Salt-Hypertensive Mice
- Author
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Yang Yao, Yun Hao, Lei Huang, Ruiping Cai, Ming-Sheng Zhou, and Yueyang Liu
- Subjects
Male ,0301 basic medicine ,Interleukin-1beta ,Gene Expression ,Blood Pressure ,Acetates ,Sodium Chloride ,030204 cardiovascular system & hematology ,Muscle hypertrophy ,Mice ,0302 clinical medicine ,Enos ,Endothelial dysfunction ,Desoxycorticosterone ,Aorta ,Chemokine CCL2 ,Mice, Knockout ,biology ,Heart ,General Medicine ,medicine.anatomical_structure ,Cardiovascular Diseases ,Hypertension ,NADPH Oxidase 2 ,Medicine ,Tumor necrosis factor alpha ,medicine.symptom ,Research Article ,medicine.medical_specialty ,Article Subject ,Nitric Oxide Synthase Type III ,Endothelium ,Inflammation ,General Biochemistry, Genetics and Molecular Biology ,Proinflammatory cytokine ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,General Immunology and Microbiology ,Tumor Necrosis Factor-alpha ,business.industry ,NADPH Oxidases ,Cytochrome b Group ,medicine.disease ,biology.organism_classification ,Mice, Inbred C57BL ,MicroRNAs ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,biology.protein ,Salts ,Endothelium, Vascular ,P22phox ,business - 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.
- Published
- 2020