亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

LPA 2 Contributes to Vascular Endothelium Homeostasis and Cardiac Remodeling After Myocardial Infarction

内科学 基因剔除小鼠 心肌梗塞 医学 平衡 内分泌学 心功能曲线 心脏纤维化 溶血磷脂酸 内皮 受体 纤维化 心力衰竭
作者
Jianqiu Pei,Lin Cai,Fang Wang,Chuansheng Xu,Shengqiang Pei,Hongwei Guo,Xiaogang Sun,Jerold Chun,Xiangfeng Cong,Weiquan Zhu,Zhe Zheng,Xi Chen
出处
期刊:Circulation Research [Lippincott Williams & Wilkins]
卷期号:131 (5): 388-403 被引量:38
标识
DOI:10.1161/circresaha.122.321036
摘要

Rationale: Myocardial infarction (MI) is one of the most dangerous adverse cardiovascular events. Our previous study found that lysophosphatidic acid (LPA) is increased in human peripheral blood after MI, and LPA has a protective effect on the survival and proliferation of various cell types. However, the role of LPA and its receptors in MI is less understood. Objectives: To study the unknown role of LPA and its receptors in heart during MI. Methods and Results: In this study, we found that mice also had elevated LPA level in peripheral blood, as well as increased cardiac expression of its receptor LPA 2 in the early stages after MI. With adult and neonate MI models in global Lpar2 knockout ( Lpar2 -KO) mice, we found Lpar2 deficiency increased vascular leak leading to disruption of its homeostasis, so as to impaired heart function and increased early mortality. Histological examination revealed larger scar size, increased fibrosis, and reduced vascular density in the heart of Lpar2 -KO mice. Furthermore, Lpar2 -KO also attenuated blood flow recovery after femoral artery ligation with decreased vascular density in gastrocnemius. Our study revealed that Lpar2 was mainly expressed and altered in cardiac endothelial cells during MI, and use of endothelial-specific Lpar2 knockout mice phenocopied the global knockout mice. Additionally, adenovirus- Lpar2 and pharmacologically activated LPA 2 significantly improved heart function, reduced scar size, increased vascular formation, and alleviated early mortality by maintaining vascular homeostasis owing to protecting vessels from leakage. Mechanistic studies demonstrated that LPA-LPA 2 signaling could promote endothelial cell proliferation through PI3K-Akt/PLC-Raf1-Erk pathway and enhanced endothelial cell tube formation via PKD1-CD36 signaling. Conclusions: Our results indicate that endothelial LPA-LPA 2 signaling promotes angiogenesis and maintains vascular homeostasis, which is vital for restoring blood flow and repairing tissue function in ischemic injuries. Targeting LPA-LPA 2 signal might have clinical therapeutic potential to protect the heart from ischemic injury.
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
PDF的下载单位、IP信息已删除 (2025-6-4)

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
yueying完成签到,获得积分10
2秒前
4秒前
Owen应助尊敬夜南采纳,获得10
7秒前
花凉完成签到,获得积分10
17秒前
花凉发布了新的文献求助20
19秒前
Ava完成签到,获得积分10
24秒前
liudy完成签到,获得积分10
37秒前
Ava发布了新的文献求助50
37秒前
吃了吃了完成签到,获得积分10
38秒前
liudy发布了新的文献求助10
43秒前
领导范儿应助科研通管家采纳,获得10
49秒前
1分钟前
阿紫吖完成签到 ,获得积分10
1分钟前
过时的白曼完成签到,获得积分10
1分钟前
隐形曼青应助三叔采纳,获得10
1分钟前
2分钟前
陈苗发布了新的文献求助10
2分钟前
在水一方应助scholar丨崔采纳,获得10
2分钟前
不能随便完成签到,获得积分10
2分钟前
2分钟前
碧蓝香芦完成签到 ,获得积分10
2分钟前
scholar丨崔发布了新的文献求助10
2分钟前
2分钟前
2分钟前
可爱的函函应助陈苗采纳,获得10
2分钟前
北北完成签到 ,获得积分10
3分钟前
3分钟前
3分钟前
Nowind发布了新的文献求助10
3分钟前
三叔发布了新的文献求助10
3分钟前
三叔完成签到,获得积分0
3分钟前
怕孤单的绿柏完成签到,获得积分10
3分钟前
Augustines完成签到,获得积分10
3分钟前
3分钟前
lijunliang完成签到 ,获得积分10
4分钟前
Lucas应助欣喜的以丹采纳,获得10
4分钟前
爱吃煎饼果子的芋圆完成签到 ,获得积分10
4分钟前
4分钟前
小神仙完成签到 ,获得积分10
4分钟前
尊敬夜南发布了新的文献求助10
4分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 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 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3990022
求助须知:如何正确求助?哪些是违规求助? 3532092
关于积分的说明 11256327
捐赠科研通 3270943
什么是DOI,文献DOI怎么找? 1805140
邀请新用户注册赠送积分活动 882270
科研通“疑难数据库(出版商)”最低求助积分说明 809228