Flow-induced reprogramming of endothelial cells in atherosclerosis

医学 内皮功能障碍 内皮干细胞 内皮 重编程 炎症 细胞生物学 血管生成 内皮细胞活化 癌症研究 免疫学 内科学 细胞 生物 干细胞 祖细胞 体外 生物化学 遗传学
作者
Ian A. Tamargo,Kyung In Baek,Yerin Kim,Christian Park,Hanjoong Jo
出处
期刊:Nature Reviews Cardiology [Springer Nature]
卷期号:20 (11): 738-753 被引量:60
标识
DOI:10.1038/s41569-023-00883-1
摘要

Atherosclerotic diseases such as myocardial infarction, ischaemic stroke and peripheral artery disease continue to be leading causes of death worldwide despite the success of treatments with cholesterol-lowering drugs and drug-eluting stents, raising the need to identify additional therapeutic targets. Interestingly, atherosclerosis preferentially develops in curved and branching arterial regions, where endothelial cells are exposed to disturbed blood flow with characteristic low-magnitude oscillatory shear stress. By contrast, straight arterial regions exposed to stable flow, which is associated with high-magnitude, unidirectional shear stress, are relatively well protected from the disease through shear-dependent, atheroprotective endothelial cell responses. Flow potently regulates structural, functional, transcriptomic, epigenomic and metabolic changes in endothelial cells through mechanosensors and mechanosignal transduction pathways. A study using single-cell RNA sequencing and chromatin accessibility analysis in a mouse model of flow-induced atherosclerosis demonstrated that disturbed flow reprogrammes arterial endothelial cells in situ from healthy phenotypes to diseased ones characterized by endothelial inflammation, endothelial-to-mesenchymal transition, endothelial-to-immune cell-like transition and metabolic changes. In this Review, we discuss this emerging concept of disturbed-flow-induced reprogramming of endothelial cells (FIRE) as a potential pro-atherogenic mechanism. Defining the flow-induced mechanisms through which endothelial cells are reprogrammed to promote atherosclerosis is a crucial area of research that could lead to the identification of novel therapeutic targets to combat the high prevalence of atherosclerotic disease. In this Review, Jo and colleagues discuss blood flow-induced mechanisms involved in endothelial cell dysfunction and atherosclerosis, including the emerging concept of disturbed-flow-induced reprogramming of endothelial cells as a pro-atherogenic mechanism, and highlight the therapeutic potential of targeting of flow-sensitive genes, proteins and pathways.
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
Jiahui完成签到,获得积分10
3秒前
香蕉觅云应助星有灵溪采纳,获得10
4秒前
骨道发布了新的文献求助10
5秒前
微笑的芯完成签到 ,获得积分10
5秒前
赘婿应助沙丁鹌鹑采纳,获得10
6秒前
许七安发布了新的文献求助10
6秒前
Billy应助lili采纳,获得30
8秒前
11秒前
贝贝发布了新的文献求助10
13秒前
在水一方应助天润佳苑采纳,获得10
13秒前
13秒前
17秒前
酷波er应助耍酷的小海豚采纳,获得30
17秒前
17秒前
自信白梦完成签到,获得积分20
17秒前
思源应助ordin采纳,获得10
18秒前
斯文败类应助Jason采纳,获得10
19秒前
星有灵溪发布了新的文献求助10
19秒前
19秒前
20秒前
20秒前
sERING发布了新的文献求助10
22秒前
沙丁鹌鹑发布了新的文献求助10
22秒前
一静齐眉完成签到,获得积分20
23秒前
CodeCraft应助steforeca采纳,获得10
23秒前
23秒前
24秒前
25秒前
26秒前
田様应助沙丁鹌鹑采纳,获得10
27秒前
嗯哼应助兆渊采纳,获得10
27秒前
黄小慧发布了新的文献求助10
27秒前
kuzzi发布了新的文献求助30
28秒前
星有灵溪完成签到,获得积分10
28秒前
彭于晏应助愛迪采纳,获得10
28秒前
29秒前
hzb发布了新的文献求助10
29秒前
Arjun应助香蕉君达采纳,获得50
30秒前
可靠的大美完成签到,获得积分10
30秒前
高分求助中
The late Devonian Standard Conodont Zonation 2000
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
Very-high-order BVD Schemes Using β-variable THINC Method 830
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
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 3248513
求助须知:如何正确求助?哪些是违规求助? 2891903
关于积分的说明 8269128
捐赠科研通 2559920
什么是DOI,文献DOI怎么找? 1388768
科研通“疑难数据库(出版商)”最低求助积分说明 650897
邀请新用户注册赠送积分活动 627798