PMID- 36497143
OWN - NLM
STAT- MEDLINE
DCOM- 20221229
LR  - 20221229
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 23
DP  - 2022 Dec 1
TI  - Normoxic HIF-1alpha Stabilization Caused by Local Inflammatory Factors and Its 
      Consequences in Human Coronary Artery Endothelial Cells.
LID - 10.3390/cells11233878 [doi]
LID - 3878
AB  - Knowledge about normoxic hypoxia-inducible factor (HIF)-1alpha stabilization is 
      limited. We investigated normoxic HIF-1alpha stabilization and its consequences using 
      live cell imaging, immunoblotting, Bio-Plex multiplex immunoassay, 
      immunofluorescence staining, and barrier integrity assays. We demonstrate for the 
      first time that IL-8 and M-CSF caused HIF-1alpha stabilization and translocation into 
      the nucleus under normoxic conditions in both human coronary endothelial cells 
      (HCAECs) and HIF-1alpha-mKate2-expressing HEK-293 cells. In line with the current 
      literature, our data show significant normoxic HIF-1alpha stabilization caused by 
      TNF-alpha, INF-gamma, IL-1beta, and IGF-I in both cell lines, as well. Treatment with a 
      cocktail consisting of TNF-alpha, INF-gamma, and IL-1beta caused significantly stronger 
      HIF-1alpha stabilization in comparison to single treatments. Interestingly, this 
      cumulative effect was not observed during simultaneous treatment with IL-8, 
      M-CSF, and IGF-I. Furthermore, we identified two different kinetics of HIF-1alpha 
      stabilization under normoxic conditions. Our data demonstrate elevated protein 
      levels of HIF-1alpha-related genes known to be involved in the development of 
      atherosclerosis. Moreover, we demonstrate an endothelial barrier dysfunction in 
      HCAECs upon our treatments and during normoxic HIF-1alpha stabilization comparable to 
      that under hypoxia. This study expands the knowledge of normoxic HIF-1alpha 
      stabilization and activation and its consequences on the endothelial secretome 
      and barrier function. Our data imply an active role of HIF-1alpha in vivo in the 
      vasculature in the absence of hypoxia.
FAU - Abdi Sarabi, Mohsen
AU  - Abdi Sarabi M
AUID- ORCID: 0000-0002-4042-6474
AD  - Department of Internal Medicine, Division of Cardiology and Angiology, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
FAU - Shiri, Alireza
AU  - Shiri A
AUID- ORCID: 0000-0002-2047-8963
AD  - Department of Internal Medicine, Division of Cardiology and Angiology, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
FAU - Aghapour, Mahyar
AU  - Aghapour M
AD  - Department of Internal Medicine, Division of Cardiology and Angiology, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
AD  - Infection Immunology Group, Institute of Medical Microbiology and Hospital 
      Hygiene, Otto-von-Guericke University, 39120 Magdeburg, Germany.
FAU - Reichardt, Charlotte
AU  - Reichardt C
AD  - Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
FAU - Brandt, Sabine
AU  - Brandt S
AUID- ORCID: 0000-0003-1912-6941
AD  - Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
FAU - Mertens, Peter R
AU  - Mertens PR
AUID- ORCID: 0000-0002-9055-6728
AD  - Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
FAU - Medunjanin, Senad
AU  - Medunjanin S
AD  - Department of Internal Medicine, Division of Cardiology and Angiology, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
FAU - Bruder, Dunja
AU  - Bruder D
AD  - Infection Immunology Group, Institute of Medical Microbiology and Hospital 
      Hygiene, Otto-von-Guericke University, 39120 Magdeburg, Germany.
AD  - Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 
      Braunschweig, Germany.
FAU - Braun-Dullaeus, Ruediger C
AU  - Braun-Dullaeus RC
AD  - Department of Internal Medicine, Division of Cardiology and Angiology, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
FAU - Weinert, Sonke
AU  - Weinert S
AUID- ORCID: 0000-0002-7201-0836
AD  - Department of Internal Medicine, Division of Cardiology and Angiology, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
LA  - eng
GR  - RTG 2408-361210922, Projects P2, P6 and P8/Deutsche Forschungsgemeinschaft/
PT  - Journal Article
DEP - 20221201
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 0 (Interleukin-8)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SB  - IM
MH  - Humans
MH  - Coronary Vessels
MH  - *Endothelial Cells/metabolism
MH  - HEK293 Cells
MH  - Hypoxia/metabolism
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Interleukin-8/metabolism
MH  - Macrophage Colony-Stimulating Factor/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
PMC - PMC9737288
OTO - NOTNLM
OT  - coronary artery endothelial dysfunction
OT  - early atherosclerosis
OT  - micromilieu factors
OT  - normoxic HIF-1alpha stabilization
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/12 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/12/01
CRDT- 2022/12/11 01:03
PHST- 2022/10/12 00:00 [received]
PHST- 2022/11/28 00:00 [revised]
PHST- 2022/11/29 00:00 [accepted]
PHST- 2022/12/11 01:03 [entrez]
PHST- 2022/12/12 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/12/01 00:00 [pmc-release]
AID - cells11233878 [pii]
AID - cells-11-03878 [pii]
AID - 10.3390/cells11233878 [doi]
PST - epublish
SO  - Cells. 2022 Dec 1;11(23):3878. doi: 10.3390/cells11233878.