Azilsartan ameliorates ox-LDL-induced endothelial dysfunction via promoting the expression of KLF2

Li, Wenfeng; Wang, Chenggao; Zhang, Dandan; Zeng, Kanghua; Xiao, Shihui; Chen, Feng; Luo, Jun

doi:10.18632/aging.202973

Cited by 12 publications

(6 citation statements)

References 32 publications

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“…KLF2 is a crucial transcriptional factor downregulated by oxLDL ( 73 ). However, the novel anti-hypertensive agent, azilsartan, prevents oxLDL-induced endothelial monolayer hyperpermeability by increasing the expression of KLF2 and occludin.…”

Section: Oxldl and Endothelial Cell Dysfunctionmentioning

confidence: 99%

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Jiang

Zhou

Nabavi³

et al. 2022

Front. Cardiovasc. Med.

108

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Atherosclerosis is an immuno-metabolic disease involving chronic inflammation, oxidative stress, epigenetics, and metabolic dysfunction. There is compelling evidence suggesting numerous modifications including the change of the size, density, and biochemical properties in the low-density lipoprotein (LDL) within the vascular wall. These modifications of LDL, in addition to LDL transcytosis and retention, contribute to the initiation, development and clinical consequences of atherosclerosis. Among different atherogenic modifications of LDL, oxidation represents a primary modification. A series of pathophysiological changes caused by oxidized LDL (oxLDL) enhance the formation of foam cells and atherosclerotic plaques. OxLDL also promotes the development of fatty streaks and atherogenesis through induction of endothelial dysfunction, formation of foam cells, monocyte chemotaxis, proliferation and migration of SMCs, and platelet activation, which culminate in plaque instability and ultimately rupture. This article provides a concise review of the formation of oxLDL, enzymes mediating LDL oxidation, and the receptors and pro-atherogenic signaling pathways of oxLDL in vascular cells. The review also explores how oxLDL functions in different stages of endothelial dysfunction and atherosclerosis. Future targeted pathways and therapies aiming at reducing LDL oxidation and/or lowering oxLDL levels and oxLDL-mediated pro-inflammatory responses are also discussed.

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Section: Oxldl and Endothelial Cell Dysfunctionmentioning

confidence: 99%

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Jiang

Zhou

Nabavi³

et al. 2022

Front. Cardiovasc. Med.

108

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“…KLF2 is a regulatory transcriptional factor mediating TJ protein levels [ 25 ]. KLF2 ( Figure 7 ) was found memorably downregulated in the ANG/HS-challenged HrGECs monolayer but signally upregulated by 2.5 and 5 μM Azilsartan, implying an involvement of KLF2 in the function of Azilsartan.…”

Section: Resultsmentioning

confidence: 99%

Azilsartan improves urinary albumin excretion in hypertension mice

Cao,

Zhang,

et al. 2024

Aging

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Hypertension is one of the most important risk factors for chronic kidney diseases, leading to hypertensive nephrosclerosis, including excessive albuminuria. Azilsartan, an angiotensin II type 1 receptor blocker, has been widely used for the treatment of hypertension. However, the effects of Azilsartan on urinary albumin excretion in hypertension haven’t been reported before. In this study, we investigated whether Azilsartan possesses a beneficial property against albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Compared to the control group, the ANG/HS group had higher blood pressure, oxidative stress, and inflammatory response, all of which were rescued by Azilsartan dose-dependently. Importantly, the ANG/HS-induced increase in urinary albumin excretion and decrease in the expression of occludin were reversed by Azilsartan. Additionally, it was shown that increased fluorescence intensity of FITC-dextran, declined trans-endothelial electrical resistance (TEER) values, and reduction of occludin and krüppel-like factor 2 (KLF2) were observed in ANG/HS-treated human renal glomerular endothelial cells (HrGECs), then prevented by Azilsartan. Moreover, the regulatory effect of Azilsartan on endothelial monolayer permeability in ANG/HS-treated HrGECs was abolished by the knockdown of KLF2, indicating KLF2 is required for the effect of Azilsartan. We concluded that Azilsartan alleviated diabetic nephropathy-induced increase in Uterine artery embolization (UAE) mediated by the KLF2/occludin axis.

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“…At present, research has shown that LDL-C is the main substance that leads to vascular endothelial dysfunction. LDL-C can interact with extracellular matrix, causing chronic inflammation and inducing vascular endothelial injury ( 34 ). At the same time, lipid metabolism disorders can aggravate oxidative stress, lead to the accumulation of reactive oxygen species (ROS) in the body and oxidize LDL-C to form oxidized LDL (ox-LDL), which participates in the occurrence and development of various cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the correlation between fetuin-B levels and essential hypertension: a cross-sectional study

Gao,

Liu,

et al. 2023

Endocrine Connections

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Background: Fetuin-B, a cytokine that regulates lipid metabolism, has recently been linked to cardiovascular diseases (CVDs) such as coronary heart disease. In this study, we discussed the relationship between fetuin-B and essential hypertension. Method: A bioinformatics analysis of fetuin-B was performed. A total of 206 with essential hypertension (EH) and 180 age-and-sex-matched healthy subjects (NT) were enrolled. Plasma fetuin-B, endothelin-1 (ET-1), nitric oxide (NO) and adiponectin (ADI) levels were measured using ELISA kits. Results: Bioinformatics analysis has revealed that fetuin-B plays an important role in pathways such as lipid metabolism. Compared with healthy subjects, serum fetuin-B levels in patients with essential hypertension were significantly increased. Correlation analysis showed that the serum fetuin-B level was positively correlated with SBP, DBP, BMI, FAT, WHR, IMT, LDL-C, GGT, ALT, albumin, FBG, glycated hemoglobin, and ET-1 in the overall study subjects (all P < 0.05) and negatively correlated with HDL-C, ADI, and NO (All P < 0.05). Multivariate linear regression analysis showed that SBP, FBG, LDL-C, ADI, and ET-1 were independent factors affecting serum fetuin-B. A binary logistic regression analysis showed that fetuin-B was an independent risk factor for primary hypertension (OR: 1.060, 95%CI: 1.034–1.086, P < 0.001). ROC curve analysis was used to evaluate the predictive value of fetuin-B for primary hypertension, and the optimal cutoff point was 83.14 μg/mL (sensitivity 77.4%, specificity 63.3%) (AUC) = 0.7738, 95% CI 0.7276–0.8200, P < 0.001). Conclusion: Elevated fetuin-B levels are associated with an increased risk of essential hypertension.

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Azilsartan ameliorates ox-LDL-induced endothelial dysfunction via promoting the expression of KLF2

Cited by 12 publications

References 32 publications

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Azilsartan improves urinary albumin excretion in hypertension mice

Evaluation of the correlation between fetuin-B levels and essential hypertension: a cross-sectional study

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