Losartan Attenuates Atherosclerosis in Uremic Mice by Regulating Treg/Th17 Balance via Mediating PTEN/PI3K/Akt Pathway

Wei, Shanzhai; Sun, Jie; Li, Yibei; Xu, Kangchun; Wang, Man; Zhang, Yilai

doi:10.1159/000521770

Cited by 4 publications

(5 citation statements)

References 43 publications

(45 reference statements)

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“…While the serum Treg cell frequencies, mRNA expression of Foxp3, and serum levels of the anti-inflammatory cytokines TGF-β and IL-10 were significantly reduced in CAD group, markedly enhanced frequencies of Th17 cells were observed in patients with coronary atherosclerosis, accompanied by higher levels of RORC mRNA expression and the serum proinflammatory cytokines IL-1β, IL-17, and IL-23 (p < 0.05). These results concur with those of Potekhina, Wei, and other researchers' work [17,18]. Given that the immunologic feature of atherosclerosis always manifests as the upregulation of proinflammatory cytokines and downregulation of anti-inflammatory cytokines, it can be concluded from our results that Treg/Th17 imbalance and inflammatory disequilibrium engage in the onset and progression of atherosclerosis.…”

Section: Discussionsupporting

confidence: 93%

Negative Correlation between Serum NLRP3 and the Ratio of Treg/Th17 in Patients with Obstructive Coronary Artery Disease

Fan¹,

Huang²,

Wu³

et al. 2022

Rev. Cardiovasc. Med.

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Background: Regulatory T (Treg) cells are a class of anti-inflammatory lymphocyte subpopulations with a potential protective effect against atherosclerosis, whereas T helper 17 (Th17) cells have been reported to possess proatherogenic activity. It was believed that disturbed circulating Treg/Th17 balance was associated with the onset and progression of atherosclerosis. This study is designed to probe the regulative action of serum Nod-like receptor protein 3 (NLRP3) on the Treg/Th17 balance in patients with atherosclerosis. Methods: Fifty-two patients with coronary atherosclerosis and stenosis degrees of more than 50% were assigned to the coronary artery disease (CAD) group, and an equal number of people without coronary atherosclerosis were assigned to the control group (assessed by coronary angiography). Peripheral blood mononuclear cells (PBMCs) from two group patients were extracted and cultivated. The calculation of the Treg/Th17 ratio and quantitative analysis of the Treg and Th17 cell frequencies were performed through flow cytometry. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was executed for the quantitative mRNA detection of the fork headwinged helix transcription factor (Foxp3) and the retinoic acid-related orphan nuclear receptor C (RORC) in PBMCs. Enzyme-linked immunosorbent assays were applied to measure the serum level of NLRP3, interleukin (IL)-10, IL-1β, IL-17A, IL-23, and transforming growth factor (TGF)-β1. Additionally, the connection between serum Treg/Th17 ratio and NLRP3 levels was analyzed using the Pearson correlation coefficient. Results: The baseline parameters, including sex, age, or blood biochemical indices had no difference in both groups (p > 0.05). The CAD group showed higher Th17 cell frequency, lower Treg cell frequency, and a lower Treg/Th17 ratio when compared to the control (p < 0.05). Consistent with the variation in the T-cell subset ratio, in patients with atherosclerosis, the Th17cell-related transcription factor RORC showed a markedly higher mRNA level (p < 0.05), conversely, the mRNA expression of the Treg cell-related transcription factor Foxp3 was notably reduced (p < 0.05). Similarly, the serum levels of NLRP3, IL-17A, IL-1, and IL-23 were significantly enhanced in CAD group but IL-10 and TGF-β1 were reduced (p < 0.05). Additionally, a negative correlation was found between NLRP3 and the Treg/Th17 ratio (r = -0.69, p < 0.001). Conclusions: Due to the potential impact on the serum Treg/Th17 ratio, NLRP3 may act as an aggravator in the onset and progression of atherosclerotic disease.

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Section: Discussionsupporting

confidence: 93%

Negative Correlation between Serum NLRP3 and the Ratio of Treg/Th17 in Patients with Obstructive Coronary Artery Disease

Fan¹,

Huang²,

Wu³

et al. 2022

Rev. Cardiovasc. Med.

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“…In the current study, Th17 cells but not Th1 and Th2 cells at baseline, D1, D3, and D7 were positively correlated with AIS recurrence and mortality. The potential explanations might be that: (1) Th17 cells were able to promote immune dysregulation and neuroinflammation, as well as accelerate atherosclerosis 24,25,30 ; therefore, AIS patients with increased Th17 cells might face more risk of recurrence and death; (2) Th17 cells could promote brain injury through regulating neurovascular dysfunction and blood–brain barrier disruption, which lead to poor prognosis in AIS patients 5,31 ; (3) Th1 cells might be weakly correlated with neuroinflammation in AIS 24 ; thus, they were not correlated with prognosis among AIS patients, which needed further exploration; and (4) Th2 cells were not related to disease severity and cognitive impairment (above‐mentioned); therefore, they were not associated with prognosis among AIS patients. Thus, Th17 cells but not Th1 or Th2 cells were elevated in recurrent and dead AIS patients.…”

Section: Discussionmentioning

confidence: 99%

“…The potential explanations might be that: (1) Th17 cells were able to promote immune dysregulation and neuroinflammation, as well as accelerate atherosclerosis 24,25,30 ; therefore, AIS patients with increased…”

Section: Ta B L E 3 Correlation Of Th Cells With Cognitive Impairment...mentioning

confidence: 99%

Longitudinal change of Th1, Th2, and Th17 cells and their relationship between cognitive impairment, stroke recurrence, and mortality among acute ischemic stroke patients

Cui

Han

et al. 2022

Clinical Laboratory Analysis

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Background T‐helper (Th) cells regulate immunity and inflammation, and modulate cognitive impairment in both cardio‐cerebrovascular and neurological diseases. This study aimed to explore the correlation of longitudinal change of Th1/2/17 cells with cognitive impairment and prognosis in acute ischemic stroke (AIS). Methods Th1/2/17 cells were detected by flow cytometry in peripheral blood samples from 150 AIS patients at admission (baseline), Day (D)1, D3, and D7 after admission, and from 30 controls. Mini‐Mental State Examination (MMSE) score among AIS patients at discharge was assessed. Stroke recurrence and mortality were evaluated. Results Th1 (p = 0.013) and Th17 cells (p < 0.001) but not Th2 cells (p = 0.105) were elevated in AIS patients versus controls. Th1 cells (p = 0.027) and Th17 cells (p < 0.001) but not Th2 cells (p = 0.227) were positively correlated with NIHSS score in AIS patients. Furthermore, Th1 and Th17 cells elevated from baseline to D3 and then decreased on D7 after AIS onset, while Th2 cells illustrated an opposite trend (all p < 0.001). Th17 cells on D1 (p = 0.011), D3 (p = 0.014), and D7 (p < 0.001) were correlated with lower MMSE score, and their levels on D3 (p = 0.033) and D7 (p = 0.004) were related to elevated cognitive impairment. Th1 and Th2 cells were not related to cognitive function (all p > 0.05). Additionally, Th17 cells at baseline, D1, D3, and D7 (all p < 0.05) were increased in recurrent patients versus non‐recurrent patients, and in survived patients versus dead patients, but Th1 or Th2 cells did not vary (all p > 0.05). Conclusion Th17 cells correlate with increased cognitive impairment, stroke recurrence, and mortality among AIS patients.

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“…It has been suggested that MALT1 is a potential regulator of atherosclerosis. For example, previous studies demonstrated that MALT1 could positively regulate the differentiation of T helper 17 (Th17) cells, a vital class of immune cells involved in promoting atherosclerosis progression ( 28 , 29 ). Additionally, MALT1 could also activate NF-κB signaling, which in turn induced inflammation to positively regulate atherosclerosis ( 13 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

MALT1 accelerates proatherogenic vascular smooth muscle cell growth, invasion and synthetic phenotype switching via nuclear factor‑κB signaling‑dependent way

Zheng

Bai

2023

Exp Ther Med

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Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) modulates T helper cell differentiation and nuclear factor-κB (NF-κB) pathway-mediated inflammation and potentially regulates lipid metabolism, which are all critical factors involved in atherosclerosis. The present study aimed to investigate the effect of MALT1 on the cellular functions of proatherogenic vascular smooth muscle cells (VSMCs). Therefore, to establish a human proatherogenic VSMC model, VSMCs were treated with different doses of oxidized low-density lipoprotein (oxLDL). Subsequently, the effect of MALT1 overexpression or knockdown in proatherogenic VSMCs treated with or without NF-κB activator was also explored. The results showed that treatment of proatherogenic VSMCs with oxLDL significantly elevated the mRNA and protein expression levels of MALT1 in a dose-dependent manner. Furthermore, MALT1 overexpression enhanced cell viability, invasion and phenotype switching and reduced apoptosis in proatherogenic VSMCs. However, MALT1 knockdown exerted the opposite effect on the above cellular functions. Additionally, the results revealed that MALT1 could positively regulate the NF-κB pathway in proatherogenic VSMCs. Moreover, treatment of proatherogenic VSMCs with NF-κB activator not only exacerbated the dysregulation of cellular functions, but also hampered the effect of MALT1 knockdown on attenuating cell growth, invasion and synthetic phenotype switching, thus suggesting that NF-κB was essential for the regulation of MALT1-triggered functions in proatherogenic VSMCs. In conclusion, the current study suggested that MALT1 could exacerbate cell viability, mobility and synthetic phenotype switching of proatherogenic VSMCs in a NF-κB signaling-dependent manner. Therefore, MALT1 could be considered as a potential therapeutic target for atherosclerosis.

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Losartan Attenuates Atherosclerosis in Uremic Mice by Regulating Treg/Th17 Balance via Mediating PTEN/PI3K/Akt Pathway

Cited by 4 publications

References 43 publications

Negative Correlation between Serum NLRP3 and the Ratio of Treg/Th17 in Patients with Obstructive Coronary Artery Disease

Negative Correlation between Serum NLRP3 and the Ratio of Treg/Th17 in Patients with Obstructive Coronary Artery Disease

Longitudinal change of Th1, Th2, and Th17 cells and their relationship between cognitive impairment, stroke recurrence, and mortality among acute ischemic stroke patients

MALT1 accelerates proatherogenic vascular smooth muscle cell growth, invasion and synthetic phenotype switching via nuclear factor‑κB signaling‑dependent way

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