Profiling the L-arginine/arginase 1 metabolism in early and advanced atherosclerosis

精氨酸酶 医学 精氨酸 仿形(计算机编程) 生物化学 氨基酸 化学 计算机科学 操作系统
作者
Yuting Wu,Katrin Nitz,B Bazioti,Edzard Schwedhelm,Cecilia Assunta Bonfiglio,Vasiliki Triantafyllidou,C. J. Weber,Donato Santovito,Esther Lutgens,Dorothee Atzler
出处
期刊:European Heart Journal [Oxford University Press]
卷期号:45 (Supplement_1) 被引量:1
标识
DOI:10.1093/eurheartj/ehae666.3891
摘要

Abstract Background Atherosclerosis is a chronic inflammatory disease and the primary underlying cause of cardiovascular disease (CVD). Recently, intracellular metabolic pathways have been identified as master switches of immune cell function and thus seem promising targets for therapeutic interventions aimed at lowering inflammation and thereby atherogenesis. Decades of research have demonstrated the importance of the amino acid (AA) L-arginine (Arg) in CVD. Although most research has focused on endothelium-dependent effects of Arg by the nitric oxide synthase (NOS), Arg metabolism - mainly through its metabolizing enzyme arginase 1 (Arg1) - has also been shown to regulate immune cell responses independent of its endothelial functions. Despite these findings, the cell-specific contribution of Arg/Arg1 metabolism on atherogenesis is still largely unknown. Purpose Profiling the Arg metabolism in endothelial and immune cells to identify cell-specific changes during athero-progression. Methods To investigate Arg metabolism in atherogenesis, we fed apolipoprotein E deficient (Apoe-­/­-) mice a Western diet (WD) for 6 and 12 weeks. Chow diet-fed aged-matched Apoe-­/-­ mice were used as littermate controls and C57BL/6 mice as steady-state controls. Systemic and local Arg concentrations were measured by mass-spectrometry. Arg metabolism in organs was studied by qPCR. Arg1 expression in atherosclerotic lesions was examined by immunohistochemistry (IHC). To assess cell-specific expression of Arg-related enzymes, aortic leukocytes from WD-fed Apoe-­/-­ mice were subjected to CITE-seq analysis. The role of T cell Arg1 was determined by nor-NOHA inhibition in Jurkat cells. Results AA measurements showed that systemic Arg was reduced in early and advanced atherogenesis (p<0.02), and splenic Arg was reduced in advanced atherogenesis (p=0.006) compared with steady state. In advanced atherosclerosis, Arg1 was decreased in the liver but increased in the spleen and aorta, whereas Nos2 was increased in the liver and aorta compared with steady state. To identify the cell types driving these local changes, we performed IHC on atherosclerotic lesions. Arg1+ lesional macrophages accumulated in advanced compared to early lesions (p=0.03), whereas Arg1+ endothelial cells tended to decrease (p=0.2). Surprisingly, we also found an accumulation of Arg1+ CD4+ T cells in lesions and a further upward trend with athero-progression. CITE-seq confirmed a constitutive expression of Arg1 in lymphoid clusters. In vitro experiments with Jurkat cells showed that arginase inhibition suppressed T cell proliferation and promoted apoptosis and migration (all p<0.0001). Conclusion Our data indicate that Arg metabolism is strongly regulated during athero-progression and suggest a so far unknown role of T cell-intrinsic Arg/Arg1 metabolism in the disease. Murine atherosclerosis studies are now being performed to decipher the cell-specific contribution of Arg/Arg1 metabolism in 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
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
量子星尘发布了新的文献求助10
1秒前
恋雅颖月应助幸福大白采纳,获得10
1秒前
wh完成签到,获得积分10
1秒前
余淮完成签到,获得积分10
2秒前
平淡的初翠完成签到,获得积分10
2秒前
快乐一江发布了新的文献求助10
3秒前
邱型程应助屿落采纳,获得20
4秒前
鹤鸣完成签到,获得积分10
7秒前
7秒前
7秒前
9秒前
天真的高山完成签到,获得积分10
10秒前
善良海云完成签到,获得积分10
12秒前
ANG发布了新的文献求助10
12秒前
从容梦旋完成签到,获得积分10
14秒前
15秒前
酷波er应助liuyunhao7207采纳,获得10
15秒前
人生如梦应助健忘跳跳糖采纳,获得10
16秒前
16秒前
sihanzhiyu发布了新的文献求助10
16秒前
汉堡包应助dpp采纳,获得10
16秒前
在水一方应助hnu301采纳,获得10
16秒前
jbhb完成签到,获得积分20
17秒前
Colossus完成签到,获得积分10
17秒前
17秒前
19秒前
王哒哒完成签到,获得积分10
19秒前
英姑应助Fury采纳,获得10
21秒前
善良冷松发布了新的文献求助10
21秒前
二十五完成签到,获得积分10
22秒前
王哒哒发布了新的文献求助10
23秒前
23秒前
25秒前
26秒前
29秒前
29秒前
上官若男应助善良冷松采纳,获得10
30秒前
cccyq发布了新的文献求助10
30秒前
李健应助叶叶采纳,获得30
31秒前
32秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
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 3989406
求助须知:如何正确求助?哪些是违规求助? 3531522
关于积分的说明 11254187
捐赠科研通 3270174
什么是DOI,文献DOI怎么找? 1804901
邀请新用户注册赠送积分活动 882105
科研通“疑难数据库(出版商)”最低求助积分说明 809174