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Center of Excellence In Genomic Medicine Research
Document Details
Document Type
:
Article In Journal
Document Title
:
Proangiogenic Effect of Metformin in Endothelial Cells Is via Upregulation of VEGFR1/2 and Their Signaling under Hyperglycemia-Hypoxia
Proangiogenic Effect of Metformin in Endothelial Cells Is via Upregulation of VEGFR1/2 and Their Signaling under Hyperglycemia-Hypoxia
Document Language
:
English
Abstract
:
Cardiovascular disease is the leading cause of morbidity/mortality worldwide. Metformin is the first therapy offering cardioprotection in type 2 diabetes and non-diabetic animals with unknown mechanism. We have shown that metformin improves angiogenesis via affecting expression of growth factors/angiogenic inhibitors in CD34⁺ cells under hyperglycemia-hypoxia. Now we studied the direct effect of physiological dose of metformin on human umbilical vein endothelial cells (HUVEC) under conditions mimicking hypoxia-hyperglycemia. HUVEC migration and apoptosis were studied after induction with euglycemia or hyperglycemia and/or CoCl₂ induced hypoxia in the presence or absence of metformin. HUVEC mRNA was assayed by whole transcript microarrays. Genes were confirmed by qRT-PCR, proteins by western blot, ELISA or flow cytometry. Metformin promoted HUVEC migration and inhibited apoptosis via upregulation of vascular endothelial growth factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4), ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue factor inhibitor-2 under hyperglycemia-chemical hypoxia. Therefore, metformin's dual effect in hyperglycemia-chemical hypoxia is mediated by direct effect on VEGFR1/R2 leading to activation of cell migration through MMP16 and ROCK1 upregulation, and inhibition of apoptosis by increase in phospho-ERK1/2 and FABP4, components of VEGF signaling cascades.
ISSN
:
1422-0067
Journal Name
:
International journal of molecular sciences
Volume
:
19
Issue Number
:
1
Publishing Year
:
1439 AH
2018 AD
Article Type
:
Article
Added Date
:
Monday, June 24, 2019
Researchers
Researcher Name (Arabic)
Researcher Name (English)
Researcher Type
Dr Grade
Email
Sherin Bakhashab
Bakhashab, Sherin
Researcher
Doctorate
sbakhashab@kau.edu.sa
Farid Ahmed
Ahmed, Farid
Researcher
Doctorate
fahmed1@kau.edu.sa
Hans-Juergen Schulten
Schulten, Hans-Juergen
Researcher
Doctorate
mhalqahtani@kau.edu.sa
Fahad W. Ahmed
Ahmed, Fahad W.
Researcher
Doctorate
nfahadahmed@gmail.com
Mohammed H. Al-Qahtani
Al-Qahtani, Mohammed H.
Researcher
Doctorate
mhalqahtani@kau.edu.sa
Jolanta U. Weaver
Weaver, Jolanta U.
Investigator
Doctorate
jolanta.weaver@newcastle.ac.uk
Michael Glanville
Glanville, Michael
Researcher
Doctorate
michael.glanville@newcastle.ac.uk
Files
File Name
Type
Description
44525.pdf
pdf
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