Tumor Necrosis Factor Alpha Deficiency Improves Endothelial Function and Cardiovascular Injury in Deoxycorticosterone Acetate/Salt-Hypertensive Mice

Cai, Ruiping; Huang, Yun; Liu, Yueyang; Huang, Lei; Yao, Yang; Zhou, Ming-Sheng

doi:10.1155/2020/3921074

Cited by 17 publications

(15 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…(43) In addition, studies in animal models and humans showed a protective effect of anti-TNF-α therapies on blood vessels in inflammatory and cardiovascular diseases. (44)(45)(46) Furthermore, Zhang et al (47) reported that blocking of TNF-α receptor controlled aortic atherosclerosis by reducing VCAM-1 expression in vivo. This is in agreement with the present findings that showed the significant elevation of TNF-α in the untreated rheumatoid group when compared to control group, the significant negative correlation between TNF-α and vascular reactivity and the significant positive correlation between TNF-α with VCAM-1 level.…”

Section: Discussionmentioning

confidence: 99%

Could omega-3 fatty acids preserve endothelial function in a rat model of rheumatoid arthritis?

Allam

Omar

2021

BESPS

View full text Add to dashboard Cite

Background: Endothelial dysfunction is claimed to be the cause of increased risk for cardiovascular diseases in rheumatoid arthritis (RA) patients. Omega-3 fatty acids is a promising drug in this field; however, its exact effects on endothelial functions are not fully understood. Aim of the work: This study aimed to evaluate the effect of omega-3 fatty acids on endothelial reactivity and some markers of endothelial dysfunction [Vascular cell adhesion molecule-1 (VCAM-1), tumour necrosis factor alpha (TNF-α), Malondialdehyde (MDA) and NOS activity] in a rat model of rheumatoid arthritis. Material & methods: Thirty male rats were divided into 3 groups (control, untreated RA, and RA group with omega-3 supplementation). RA induction was done by intradermal injection of heat-killed Mycobacterium butyricum and was confirmed by clinical signs of arthritis on day 11. In the treated group, omega-3 was given daily via gastric gavage starting from day 11 until the end of the study. The study duration was 30 days for all groups starting from the day of induction. At the end of the study, rats were sacrificed, blood samples were collected for VACM-1, TNF-α, MDA and nitrite measurement and thoracic aortae were taken to test vascular reactivity. Results: All markers increased while vascular reactivity decreased significantly after RA induction. Omega-3 treatment significantly decreased all biochemical markers and restored normal vascular reactivity in the treated group.

show abstract

Section: Discussionmentioning

confidence: 99%

Could omega-3 fatty acids preserve endothelial function in a rat model of rheumatoid arthritis?

Allam

Omar

2021

BESPS

View full text Add to dashboard Cite

show abstract

“…TNF α is one of the best described inflammatory cytokines in disturbed insulin signaling [ 36 , 37 ]; the infiltrating macrophages are a major source of TNF α in the vascular wall [ 18 ]. Recently, we [ 38 ] have shown that genetic knockout of TNF α gene lowers blood pressure and vascular inflammation and protects against endothelial dysfunction and vascular injury in DOCA salt-sensitive hypertension. Here, we showed that TNF α expression was significantly increased in the vasculature of hypertensive DS rats; macrophage depletion reduced vascular TNF α expression and inhibited NF κ B and JNK activation associated with the improvement of vascular insulin signaling and insulin-mediated vasorelaxation.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Depletion Improves Endothelial Insulin Resistance and Protects against Cardiovascular Injury in Salt-Sensitive Hypertension

Liu

Luo

Cai

et al. 2020

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Vascular endothelial insulin signaling is critical for the maintenance of vascular and metabolic homeostasis. We have previously shown that in hypertensive Dahl rats, impaired vascular insulin action is linked to angiotensin II activation of the NFκB inflammatory pathway. Macrophage polarization (M1) has implicated in hypertensive and metabolic diseases. Here, we investigated the effect of macrophage depletion using liposome-encapsulated clodronate (LEC) on endothelial insulin resistance and cardiovascular remodeling in Dahl salt-sensitive (DS) rats. High salt intake (HS) for 5 weeks increased systolic blood pressure (SBP: 192±5 vs. 144±4 mmHg in NS, p<0.05), aortic and cardiac hypertrophy, cardiac fibrosis, and impaired acetylcholine- and insulin-induced vasorelaxation, accompanied by impaired insulin activation of endothelial nitric oxide synthases (eNOS)/NO signaling. HS rats had a significant increase in CD68 (a monocyte/macrophage marker) expression in the aorta and the heart. LEC reduced SBP (168±5 mmHg, p<0.05) and cardiovascular injury and improved acetylcholine- and insulin-mediated vasorelaxation and insulin signaling molecules with a reduction in the macrophage infiltration in the aorta and the heart. HS rats also manifested an increase in the aortic expressions of inflammatory cytokines, including the ratio of phosphorylated inhibitory kappa B (Iκb)/Iκb, tumor necrosis factor α, and phosphorylated c-Jun N-terminal kinase (JNK) and oxidative stress, which were reduced in HS/LEC rats. Our results suggest that in salt-sensitive hypertension, macrophage may importantly contribute to endothelial insulin resistance, vascular inflammation, and injury. These findings support the idea that macrophages may be a new target for immunotherapy of vasculopathy in hypertensive and metabolic disorders.

show abstract

“…Endothelium-dependent vasorelaxation to acetylcholine or endothelium-independent relaxation to sodium nitroprusside was determined using an organ bath chamber (DMT Inc., Denmark) as previously described (Cai et al, 2020). The thoracic aorta was cut into 3-mm aortic rings, and the aortic rings were contracted twice with KPSS solution containing 60 mmol/L KCL.…”

Section: Organ Chamber Experimentsmentioning

confidence: 99%

“…The classically activated M1 macrophages are usually produced during cell-mediated host immune response and typically induced by lipopolysaccharide (LPS) or Th1 cytokines, such as tumor necrosis factor (TNF)α and interferon (IFN)γ (Zhang et al, 2012;Dungan et al, 2014;Orecchioni et al, 2019). M1 macrophages are more susceptible to the migration of the vascular wall and the release of inflammatory cytokines, such as TNFα and interleukin (IL)-1β, which may initiate vascular inflammation, oxidative stress, and vascular damage (Cai et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Myeloid Angiotensin II Type 1 Receptor Mediates Macrophage Polarization and Promotes Vascular Injury in DOCA/Salt Hypertensive Mice

et al. 2022

Self Cite

View full text Add to dashboard Cite

Activation of the renin–angiotensin system has been implicated in hypertension. Angiotensin (Ang) II is a potent proinflammatory mediator. The present study investigated the role of myeloid angiotensin type 1 receptor (AT1R) in control of macrophage phenotype in vitro and vascular injury in deoxycorticosterone acetate (DOCA)/salt hypertension. In human THP-1/macrophages, Ang II increased mRNA expressions of M1 cytokines and decreased M2 cytokine expressions. Overexpression of AT1R further increased Ang II-induced expressions of M1 cytokines and decreased M2 cytokines. Silenced AT1R reversed Ang II-induced changes in M1 and M2 cytokines. Ang II upregulated hypoxia-inducible factor (HIF)1α, toll-like receptor (TLR)4, and the ratio of pIκB/IκB, which were prevented by silenced AT1R. Silenced HIF1α prevented Ang II activation of the TLR4/NFκB pathway. Furthermore, Ang II increased HIF1α via reactive oxygen species-dependent reduction in prolyl hydroxylase domain protein 2 (PHD2) expression. The expressions of AT1R and HIF1α and the ratio of pIκB/IκB were upregulated in the peritoneal macrophages of DOCA hypertensive mice, and the specific deletion of myeloid AT1R attenuated cardiac and vascular injury and vascular oxidative stress, reduced the recruitment of macrophages and M1 cytokine expressions, and improved endothelial function without significant reduction in blood pressure. Our results demonstrate that Ang II/AT1R controls the macrophage phenotype via stimulating the HIF1α/NFκB pathway, and specific myeloid AT1R KO improves endothelial function, vascular inflammation, and injury in salt-sensitive hypertension. The results support the notion that myeloid AT1R plays an important role in the regulation of the macrophage phenotype, and dysfunction of this receptor may promote vascular dysfunction and injury in salt-sensitive hypertension.

show abstract

Tumor Necrosis Factor Alpha Deficiency Improves Endothelial Function and Cardiovascular Injury in Deoxycorticosterone Acetate/Salt-Hypertensive Mice

Cited by 17 publications

References 39 publications

Could omega-3 fatty acids preserve endothelial function in a rat model of rheumatoid arthritis?

Could omega-3 fatty acids preserve endothelial function in a rat model of rheumatoid arthritis?

Macrophage Depletion Improves Endothelial Insulin Resistance and Protects against Cardiovascular Injury in Salt-Sensitive Hypertension

Myeloid Angiotensin II Type 1 Receptor Mediates Macrophage Polarization and Promotes Vascular Injury in DOCA/Salt Hypertensive Mice

Contact Info

Product

Resources

About