Early growth response factor 3 may regulate coronary atherosclerosis through the NF-κB signaling pathway and VEGF expression

IF 2.3 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL American Journal of the Medical Sciences Pub Date : 2024-07-09 DOI:10.1016/j.amjms.2024.07.003
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Abstract

Aim

The present study was conducted to measure the expression of early growth response factor 3 (Egr3), inflammatory cytokines (IL-1β, IL-6), vascular endothelial growth factor (VEGF) and NF-κB in patients with coronary artery disease (CAD) to investigate the relationships of these molecules and Egr3 gene expression.

Methods

We recruited 132 CAD patients and 63 healthy individuals. The expression levels of Egr3, VEGF, p50 and p65 were measured by reverse transcription quantitative polymerase chain reaction and the levels of Egr3, IL-1β and IL-6 in patients serum and in human coronary artery endothelial cells (HCAECs) were measured by enzyme-linked immunosorbent assay (ELISAs) in CAD patients. HCAECs were treated with ox-LDL to establish an in vitro atherosclerosis model. An oil red O staining assay was used to assess the lipid droplet formation. A colloidal external lumen formed by Matrigel was used to test the migration of HCAECs. The expression of Egr3, VEGF and NF-κB was determined by Western blotting.

Results

The levels of serum Egr3 and IL-6 in the severe stenosis group were greater than those in the mild stenosis group and controls (p < 0.05). The level of serum IL-1β in the severe stenosis group was greater than that in the control group (p < 0.05). Moreover, Egr3 expression was positively associated with IL-6 levels (r = 0.55, p < 0.001), IL-1β levels (r = 0.21, p = 0.004) and the Gensini score (r = 0.20, p = 0.02). We also found that Egr3 expression was significantly greater in CAD patients than that in controls. And its expression was highest in the mild patients. The expression of VEGF, P50 and P65 was also greater in CAD patients. In the in vitro experiment, we found that the inhibition of Egr3 expression significantly reduced the expression levels of p50, p65, IL-6 and CRP. Moreover, the inhibition of Egr3 expression significantly reduced the lipid droplet formation and decreased capability of lumen formation.

Conclusions

In the pathogenesis of atherosclerosis, Egr3 gene expression may induce the expression of inflammatory factors and lipid droplet formation and lumen formation, which could promote the atherosclerosis development.
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早期生长应答因子 3 通过 NF-κB 信号通路和血管内皮生长因子的表达调控冠状动脉粥样硬化。
目的:本研究测量冠状动脉疾病(CAD)患者早期生长应答因子 3(Egr3)、炎症细胞因子(IL-1β、IL-6)、血管内皮生长因子(VEGF)和 NF-κB 的表达,以探讨这些分子与 Egr3 基因表达的关系:方法:我们招募了 132 名 CAD 患者和 63 名健康人。方法:我们招募了 132 名 CAD 患者和 63 名健康人,通过逆转录定量聚合酶链反应测定了 Egr3、VEGF、p50 和 p65 的表达水平,并通过酶联免疫吸附试验(ELISA)测定了 CAD 患者血清和人冠状动脉内皮细胞(HCAECs)中 Egr3、IL-1β 和 IL-6 的水平。用 ox-LDL 处理 HCAECs,以建立体外动脉粥样硬化模型。用油红 O 染色法评估脂滴的形成。用 Matrigel 形成的胶体外腔测试 HCAECs 的迁移。用 Western 印迹法测定 Egr3、VEGF 和 NF-κB 的表达:结果:重度狭窄组血清 Egr3 和 IL-6 水平高于轻度狭窄组和对照组(P < 0.05)。重度狭窄组的血清 IL-1β 水平高于对照组(P < 0.05)。此外,Egr3 的表达与 IL-6 水平(r= 0.55,p<0.001)、IL-1β 水平(r=0.21,p=0.004)和 Gensini 评分(r=0.20,p=0.02)呈正相关。我们还发现,Egr3 在 CAD 患者中的表达明显高于对照组。轻度患者的表达量最高。血管内皮生长因子、P50 和 P65 在 CAD 患者中的表达也更高。在体外实验中,我们发现抑制 Egr3 的表达可明显降低 p50、p65、IL-6 和 CRP 的表达水平。此外,抑制 Egr3 的表达还能明显减少脂滴的形成,降低管腔形成的能力:结论:在动脉粥样硬化的发病机制中,Egr3基因的表达可能诱导炎症因子的表达、脂滴的形成和管腔的形成,从而促进动脉粥样硬化的发展。
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索莱宝 0.1 M PMSF
索莱宝 RIPA lysis buffer
索莱宝 BCA protein kit
索莱宝 ox-LDL
上海源叶 Red O cell ORO staining
来源期刊
CiteScore
4.40
自引率
0.00%
发文量
303
审稿时长
1.5 months
期刊介绍: The American Journal of The Medical Sciences (AJMS), founded in 1820, is the 2nd oldest medical journal in the United States. The AJMS is the official journal of the Southern Society for Clinical Investigation (SSCI). The SSCI is dedicated to the advancement of medical research and the exchange of knowledge, information and ideas. Its members are committed to mentoring future generations of medical investigators and promoting careers in academic medicine. The AJMS publishes, on a monthly basis, peer-reviewed articles in the field of internal medicine and its subspecialties, which include: Original clinical and basic science investigations Review articles Online Images in the Medical Sciences Special Features Include: Patient-Centered Focused Reviews History of Medicine The Science of Medical Education.
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