PMID- 24161393 OWN - NLM STAT- MEDLINE DCOM- 20140117 LR - 20131118 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 441 IP - 2 DP - 2013 Nov 15 TI - Pigment epithelium-derived factor (PEDF) binds to caveolin-1 and inhibits the pro-inflammatory effects of caveolin-1 in endothelial cells. PG - 405-10 LID - S0006-291X(13)01755-5 [pii] LID - 10.1016/j.bbrc.2013.10.074 [doi] AB - Pigment epithelium-derived factor (PEDF) exerts atheroprotective effects both in cell culture and animal models through its anti-oxidative and anti-inflammatory properties. Caveolin-1 (Cav), a major protein component of caveolae in endothelial cells (ECs), plays a role in the progression of atherosclerosis. However, effects of PEDF on Cav-exposed ECs remain unknown. In this study, we examined whether and how PEDF could inhibit the Cav-induced inflammatory and thrombogenic reactions in human umbilical vein ECs (HUVECs). Surface plasmon resonance revealed that PEDF bound to Cav at the dissociation constant of 7.36x10(-7) M. Further, one of the major Cav-interacting proteins in human serum was identified as PEDF by peptide mass fingerprinting analysis using BIAcore 1000 combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Exogenously added Cav was taken up into the membrane fraction of HUVECs and dose-dependently increased monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1) and plasminogen activator inhibitor-1 (PAI-1) mRNA levels, all of which were blocked by the simultaneous treatment with 10nM PEDF. Small interfering RNAs directed against Cav decreased endogenous Cav levels and suppressed gene expression of MCP-1, VCAM-1 and PAI-1 in HUVECs. This study indicates that PEDF binds to Cav and could block the inflammatory and thrombogenic reactions in Cav-exposed HUVECs. Our present study suggests that atheroprotective effects of PEDF might be partly ascribed to its Cav-interacting properties. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Matsui, Takanori AU - Matsui T AD - Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. FAU - Higashimoto, Yuichiro AU - Higashimoto Y FAU - Taira, Junichi AU - Taira J FAU - Yamagishi, Sho-ichi AU - Yamagishi S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131023 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (CAV1 protein, human) RN - 0 (CCL2 protein, human) RN - 0 (Caveolin 1) RN - 0 (Chemokine CCL2) RN - 0 (Eye Proteins) RN - 0 (Nerve Growth Factors) RN - 0 (Plasminogen Activator Inhibitor 1) RN - 0 (RNA, Small Interfering) RN - 0 (Serpins) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 0 (pigment epithelium-derived factor) SB - IM MH - Atherosclerosis/genetics/*metabolism MH - Caveolin 1/genetics/*metabolism/pharmacology MH - Chemokine CCL2/genetics MH - Eye Proteins/genetics/*metabolism/pharmacology MH - Gene Expression/drug effects MH - Human Umbilical Vein Endothelial Cells/*metabolism MH - Humans MH - Inflammation/genetics/*metabolism MH - Nerve Growth Factors/genetics/*metabolism/pharmacology MH - Plasminogen Activator Inhibitor 1/genetics MH - RNA, Small Interfering/genetics MH - Serpins/genetics/*metabolism/pharmacology MH - Thrombosis/genetics/metabolism MH - Vascular Cell Adhesion Molecule-1/genetics OTO - NOTNLM OT - Caveolin-1 OT - Endothelial cells OT - Inflammation OT - MALDI-TOF mass spectrometry OT - PEDF EDAT- 2013/10/29 06:00 MHDA- 2014/01/18 06:00 CRDT- 2013/10/29 06:00 PHST- 2013/09/30 00:00 [received] PHST- 2013/10/15 00:00 [accepted] PHST- 2013/10/29 06:00 [entrez] PHST- 2013/10/29 06:00 [pubmed] PHST- 2014/01/18 06:00 [medline] AID - S0006-291X(13)01755-5 [pii] AID - 10.1016/j.bbrc.2013.10.074 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2013 Nov 15;441(2):405-10. doi: 10.1016/j.bbrc.2013.10.074. Epub 2013 Oct 23.