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 TypeDr GradeEmail
Sherin BakhashabBakhashab, Sherin ResearcherDoctoratesbakhashab@kau.edu.sa
Farid AhmedAhmed, Farid ResearcherDoctoratefahmed1@kau.edu.sa
Hans-Juergen SchultenSchulten, Hans-Juergen ResearcherDoctoratemhalqahtani@kau.edu.sa
Fahad W. AhmedAhmed, Fahad W.ResearcherDoctoratenfahadahmed@gmail.com
Mohammed H. Al-QahtaniAl-Qahtani, Mohammed H.ResearcherDoctoratemhalqahtani@kau.edu.sa
Jolanta U. WeaverWeaver, Jolanta U.InvestigatorDoctoratejolanta.weaver@newcastle.ac.uk
Michael GlanvilleGlanville, Michael ResearcherDoctoratemichael.glanville@newcastle.ac.uk

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