Imperial College London
Alternate

ProfessorDavidCarling

Faculty of Medicine, Institute of Clinical Sciences

Professor of Biochemistry
 
 
 
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Contact

 

+44 (0)7590 250 559david.carling

 
 
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Location

 

2.14DLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Seneviratne:2020:10.1161/CIRCRESAHA.119.315528,
author = {Seneviratne, A and Han, Y and Wong, E and Walter, E and Jiang, L and Cave, L and Long, NJ and Carling, D and Mason, JC and Haskard, DO and Boyle, J},
doi = {10.1161/CIRCRESAHA.119.315528},
journal = {Circulation Research},
pages = {928--944},
title = {Hematoma resolution in vivo is directed by Activating Transcription Factor 1},
url = {http://dx.doi.org/10.1161/CIRCRESAHA.119.315528},
volume = {127},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Rationale: The efficient resolution of tissue hemorrhage is an important homeostatic function. In human macrophages in vitro, heme activates an adenosine monophosphate activated protein kinase / activating transcription factor 1 (AMPK/ATF1) pathway that directs Mhem macrophages through coregulation of heme oxygenase 1 (HMOX1, HO-1) and lipid homeostasis genes.Objective: We asked whether this pathway had an in vivo role in mice.Methods and Results: Perifemoral hematomas were used as a model of hematoma resolution. In mouse bone marrow derived macrophages (mBMM), heme induced HO-1, lipid regulatory genes including LXR, the growth factor IGF1, and the splenic red pulp macrophage gene Spic. This response was lost in mBMM from mice deficient in AMPK (Prkab1-/-) or ATF1 (Atf1-/-). In vivo, femoral hematomas resolved completely between day 8 and day 9 in littermate control mice (n=12), but were still present at day 9 in mice deficient in either AMPK (Prkab1-/-) or ATF1 (Atf1-/-) (n=6 each). Residual hematomas were accompanied by increased macrophage infiltration, inflammatory activation and oxidative stress. We also found that fluorescent lipids and a fluorescent iron-analog were trafficked to lipid-laden and iron-laden macrophages respectively. Moreover erythrocyte iron and lipid abnormally colocalized in the same macrophages in Atf1-/- mice. Therefore, iron-lipid separation was Atf1-dependent.Conclusions: Taken together, these data demonstrate that both AMPK and ATF1 are required for normal hematoma resolution.
AU  - Seneviratne,A
AU  - Han,Y
AU  - Wong,E
AU  - Walter,E
AU  - Jiang,L
AU  - Cave,L
AU  - Long,NJ
AU  - Carling,D
AU  - Mason,JC
AU  - Haskard,DO
AU  - Boyle,J
DO  - 10.1161/CIRCRESAHA.119.315528
EP  - 944
PY  - 2020///
SN  - 0009-7330
SP  - 928
TI  - Hematoma resolution in vivo is directed by Activating Transcription Factor 1
T2  - Circulation Research
UR  - http://dx.doi.org/10.1161/CIRCRESAHA.119.315528
UR  - http://hdl.handle.net/10044/1/81111
VL  - 127
ER  -
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