Development of activated endothelial targeted high-density lipoprotein nanoparticles

被引：3

作者：

Yu, Minzhi ^{[1
,2
]}

Hong, Kristen ^{[1
,2
]}

Adili, Reheman ^{[3
]}

Mei, Ling ^{[1
,2
]}

Liu, Lisha ^{[1
,2
,4
]}

He, Hongliang ^{[1
,2
,5
]}

Guo, Yanhong ^{[6
]}

Chen, Y. Eugene ^{[6
]}

Holinstat, Michael ^{[3
,6
]}

Schwendeman, Anna ^{[1
,2
]}

机构：

[1] Univ Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48105 USA

[2] Univ Michigan, Biointerfaces Inst, Ann Arbor, MI 48105 USA

[3] Univ Michigan, Dept Pharmacol, Med Sch, Ann Arbor, MI USA

[4] China Pharmaceut Univ, Sch Pharm, Dept Pharmaceut, Nanjing, Peoples R China

[5] Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Bioelect, Jiangsu Key Lab Biomat & Devices, Nanjing, Peoples R China

[6] Univ Michigan, Frankel Cardiovasc Ctr, Dept Internal Med, Ann Arbor, MI USA

来源：

FRONTIERS IN PHARMACOLOGY | 2022年 / 13卷

基金：

美国国家卫生研究院;

关键词：

VCAM-1; endothelium; inflammation; anti-inflammation; high-density lipoprotein; ADHESION MOLECULE-1; CHOLESTEROL EFFLUX; E-SELECTIN; HDL; ATHEROSCLEROSIS; DYSFUNCTION; CELLS; INFLAMMATION; EXPRESSION; PARTICLES;

D O I：

10.3389/fphar.2022.902269

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Endothelial inflammation is an important pathophysiological driving force in various acute and chronic inflammatory diseases. High-density lipoproteins (HDLs) play critical roles in regulating endothelial functions and resolving endothelial inflammation. In the present study, we developed synthetic HDLs (sHDLs) which actively target inflamed endothelium through conjugating vascular cell adhesion protein 1 (VCAM-1) specific VHPK peptide. The active targeting of VHPK-sHDLs was confirmed in vitro on TNF-alpha activated endothelial cells. VHPK-sHDLs presented potent anti-inflammatory efficacies in vitro through the reduction of proinflammatory cytokine production and inhibition of leukocyte adhesion to activated endothelium. VHPK-sHDLs showed increased binding on inflamed vessels and alleviated LPS-induced lung inflammation in vivo. The activated endothelium-targeted sHDLs may be further optimized to resolve endothelial inflammation in various inflammatory diseases.

引用

页数：14