期刊
FRONTIERS IN PHARMACOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.902269
关键词
VCAM-1; endothelium; inflammation; anti-inflammation; high-density lipoprotein
资金
- National Institutes of Health
- University of Michigan Frankel Cardiovascular Center [R44 GM145103, HL134569, R21 TR003185, R35 GM131835]
- American Heart Association [G024210]
- Pharmacological Sciences Training Program [19PRE34400017]
- Translational Cardiovascular Research and Entrepreneurship Training Program [T32 GM 7767]
- [T32 HL125242]
In this study, synthetic HDLs (sHDLs) were developed to target inflamed endothelium and resolve endothelial inflammation. The sHDLs, conjugated with VHPK peptide specific to VCAM-1, showed potent anti-inflammatory effects in vitro and alleviated lung inflammation in vivo.
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.
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