PMID- 34710824
OWN - NLM
STAT- MEDLINE
DCOM- 20211228
LR  - 20221211
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 582
DP  - 2021 Dec 10
TI  - Adropin decreases endothelial monolayer permeability after cell-free hemoglobin 
      exposure and reduces MCP-1-induced macrophage transmigration.
PG  - 105-110
LID - S0006-291X(21)01439-X [pii]
LID - 10.1016/j.bbrc.2021.10.032 [doi]
AB  - BACKGROUND: Cell-free heme-containing proteins mediate endothelial injury in a 
      variety of disease states including subarachnoid hemorrhage and sepsis by 
      increasing endothelial permeability. Inflammatory cells are also attracted to 
      sites of vascular injury by monocyte chemotactic protein 1 (MCP-1) and other 
      chemokines. We have identified a novel peptide hormone, adropin, that protects 
      against hemoglobin-induced endothelial permeability and MCP-1-induced macrophage 
      migration. METHODS: Human microvascular endothelial cells were exposed to 
      cell-free hemoglobin (CFH) with and without adropin treatment before measuring 
      monolayer permeability using a FITC-dextran tracer assay. mRNA and culture media 
      were collected for molecular studies. We also assessed the effect of adropin on 
      macrophage movement across the endothelial monolayer using an MCP-1-induced 
      migration assay. RESULTS: CFH exposure decreases adropin expression and increases 
      paracellular permeability of human endothelial cells. Treating cells with 
      synthetic adropin protects against the increased permeability observed during the 
      natural injury progression. Cell viability was similar in all groups and Hmox1 
      expression was not affected by adropin treatment. MCP-1 potently induced 
      macrophage migration across the endothelial monolayer and adropin treatment 
      effectively reduced this phenomenon. CONCLUSIONS: Endothelial injury is a 
      hallmark of many disease states. Our results suggest that adropin treatment could 
      be a valuable strategy in preventing heme-mediated endothelial injury and 
      macrophage infiltration. Further investigation of adropin therapy in animal 
      models and human tissue specimens is needed.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Dodd, William S
AU  - Dodd WS
AD  - Department of Neurosurgery, College of Medicine, University of Florida, 
      Gainesville, FL, USA.
FAU - Patel, Devan
AU  - Patel D
AD  - College of Medicine, Florida State University, Tallahassee, FL, USA.
FAU - Lucke-Wold, Brandon
AU  - Lucke-Wold B
AD  - Department of Neurosurgery, College of Medicine, University of Florida, 
      Gainesville, FL, USA.
FAU - Hosaka, Koji
AU  - Hosaka K
AD  - Department of Neurosurgery, College of Medicine, University of Florida, 
      Gainesville, FL, USA.
FAU - Chalouhi, Nohra
AU  - Chalouhi N
AD  - Department of Neurosurgery, College of Medicine, University of Florida, 
      Gainesville, FL, USA.
FAU - Hoh, Brian L
AU  - Hoh BL
AD  - Department of Neurosurgery, College of Medicine, University of Florida, 
      Gainesville, FL, USA. Electronic address: brian.hoh@neurosurgery.ufl.edu.
LA  - eng
GR  - R01 NS110710/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211016
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enho protein, human)
RN  - 0 (Hemoglobins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
SB  - IM
MH  - Cell Line
MH  - Cell Membrane Permeability/drug effects
MH  - Cell Movement/*drug effects
MH  - Chemokine CCL2/*antagonists & inhibitors/pharmacology
MH  - Cytoprotection/physiology
MH  - Endothelial Cells/cytology/*drug effects/metabolism
MH  - Hemoglobins/*antagonists & inhibitors/pharmacology
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*pharmacology
MH  - Macrophages/cytology/*drug effects
PMC - PMC8890595
MID - NIHMS1779868
OTO - NOTNLM
OT  - Adropin
OT  - Endothelium
OT  - Hemoglobin
OT  - Hemorrhage
OT  - Sepsis
COIS- Declaration of competing interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Brian L. Hoh reports financial support was provided by National 
      Institutes of Health. William S. Dodd & Brian L. Hoh reports financial support 
      was provided by The Brain Aneurysm Foundation.
EDAT- 2021/10/29 06:00
MHDA- 2021/12/29 06:00
PMCR- 2022/12/10
CRDT- 2021/10/28 20:30
PHST- 2021/09/07 00:00 [received]
PHST- 2021/10/15 00:00 [accepted]
PHST- 2021/10/29 06:00 [pubmed]
PHST- 2021/12/29 06:00 [medline]
PHST- 2021/10/28 20:30 [entrez]
PHST- 2022/12/10 00:00 [pmc-release]
AID - S0006-291X(21)01439-X [pii]
AID - 10.1016/j.bbrc.2021.10.032 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2021 Dec 10;582:105-110. doi: 
      10.1016/j.bbrc.2021.10.032. Epub 2021 Oct 16.