VCAM-1-binding peptide targeted cationic liposomes containing NLRP3 siRNA to modulate LDL transcytosis as a novel therapy for experimental atherosclerosis

跨细胞 炎症体 化学 阳离子脂质体 基因敲除 体内 小干扰RNA 细胞生物学 药理学 医学 生物化学 转染 受体 生物 内吞作用 细胞凋亡 生物技术 基因
作者
Xiong Jia,Xiangli Bai,Xiaoyan Yang,Ling Wang,Yajing Lu,Lin Zhu,Ying Zhao,Wenzhuo Cheng,Shu Meng,Qiyong Mei,Si Jin
出处
期刊:Metabolism-clinical and Experimental [Elsevier]
卷期号:135: 155274-155274 被引量:11
标识
DOI:10.1016/j.metabol.2022.155274
摘要

Activation of NLRP3 inflammasome accelerates the formation of atherosclerotic plaques. Here, we evaluated the effects of inflammation on the expression of the NLRP3 inflammasome in endothelial cells (ECs).The effect of TNF-α on transcytosis of LDL was measured. VCAM-1 binding peptide targeting cationic liposomes (PCLs) were prepared as siRNA vectors. Methylated NLRP3 siRNA was encapsulated into the PCLs to knock down NLRP3 in vitro and in vivo. In rats with partial carotid ligation, TNF-α-induced LDL retention in the carotid artery endothelium was observed. In ApoE-/- mice, NLRP3 siRNA-PCLs were injected intravenously to observe their effect on the formation of atherosclerosis.Our results showed that TNF-α upregulated NLRP3 in ECs, promoting the assembly of the NLRP3 inflammasome and processing of pro-IL-1β into IL-1β. Moreover, TNF-α accelerated LDL transcytosis in ECs. Knockdown of NLRP3 prevented TNF-α-induced NLPR3 inflammasome/IL-1β signaling and LDL transcytosis. Using optimized cationic liposomes to encapsulate methylated NLRP3 siRNA, resulting in targeting of VCAM-1-expressing ECs, to knockdown NLRP3, TNF-α-induced NLRP3 inflammasome activation and LDL transcytosis were prevented. Using the partial carotid ligation as an atherosclerosis rat model, we found that local administration of NLRP3 siRNA-PCLs efficiently knocked down NLPR3 expression in the carotid endothelium and dramatically attenuated the deposition of atherogenic LDL in carotid ECs in TNF-α-challenged rats. Furthermore, NLRP3 siRNA-PCLs were injected intravenously in ApoE-/- mice, resulting in reduced plaque formation.These findings established a novel strategy for targeting the NLRP3 inflammasome using NLRP3 siRNA-PCLs to interrupt LDL transcytosis, representing a potential novel therapy for atherosclerosis.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
所所应助科研通管家采纳,获得10
3秒前
小蘑菇应助科研通管家采纳,获得10
3秒前
科研張应助科研通管家采纳,获得20
3秒前
情怀应助科研通管家采纳,获得10
3秒前
3秒前
Akim应助科研通管家采纳,获得10
4秒前
李爱国应助科研通管家采纳,获得10
4秒前
小马甲应助科研通管家采纳,获得10
4秒前
薰硝壤应助科研通管家采纳,获得10
4秒前
4秒前
4秒前
4秒前
4秒前
4秒前
丰富广缘完成签到 ,获得积分10
4秒前
陆访文发布了新的文献求助10
4秒前
科研通AI2S应助Crossover采纳,获得10
5秒前
xxx完成签到,获得积分20
6秒前
6秒前
121231233完成签到,获得积分10
7秒前
彭于彦祖应助费小曼采纳,获得50
8秒前
蓬莱山完成签到 ,获得积分10
8秒前
8秒前
lly完成签到,获得积分10
8秒前
9秒前
小C完成签到,获得积分10
9秒前
9秒前
kang12完成签到,获得积分10
9秒前
害怕的涔完成签到 ,获得积分10
9秒前
9秒前
followZ完成签到,获得积分10
10秒前
稚未完成签到,获得积分10
10秒前
四川知名猛男完成签到 ,获得积分10
10秒前
11秒前
jjdgangan发布了新的文献求助10
11秒前
Ampace小老弟发布了新的文献求助200
12秒前
13秒前
Afeng发布了新的文献求助10
13秒前
思源应助lyh采纳,获得10
13秒前
高分求助中
Evolution 10000
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
A new approach of magnetic circular dichroism to the electronic state analysis of intact photosynthetic pigments 500
Diagnostic immunohistochemistry : theranostic and genomic applications 6th Edition 500
Chen Hansheng: China’s Last Romantic Revolutionary 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3148993
求助须知:如何正确求助?哪些是违规求助? 2800076
关于积分的说明 7838336
捐赠科研通 2457543
什么是DOI,文献DOI怎么找? 1307913
科研通“疑难数据库(出版商)”最低求助积分说明 628328
版权声明 601685