Focal adhesion kinase–related pathways may be suppressed by metformin in vascular smooth muscle cells in high glucose conditions

Abstract

Cardiovascular diseases account for approximately 65 percent of deaths in patients with diabetes mellitus. 1 It is well known that the pathogenesis of atherosclerosis is related to the proliferation and migration of vascular smooth muscle cells (VSMCs) within the media layer of arteries, so that these events promote atherogenic plaques led to vessel stenosis and restenosis. Molecular mechanisms behind VSMC proliferation and migration remain unclear. 2,3 Hyperglycemia, however, is not the only factor involved in the progression of cardiovascular diseases in diabetics but it is involved in several pathways including the activation of protein kinase C, the formation of advanced glycation end-products (AGEs) and the stimulation of lipoxygenase synthesis pathway. 4

Beta arrestin‐related signalling axes are influenced by dexamethasone and metformin in vascular smooth muscle cells cultured in high glucose condition

“…FAK (PTK2), as a key gene in the chemokine signalling pathway, has recently reported to be involved in the proliferation and migration of VSMCs treated with Met 19 . BARR2 is also a nuclear internalized protein in the chemokine signalling pathway so that we proposed Met and Dexa might affect its function in VSMCs.…”

“…14,17,18 FAK (PTK2), as a key gene in the chemokine signalling pathway, has recently reported to be involved in the proliferation and migration of VSMCs treated with Met. 19 BARR2 is also a nuclear internalized protein in the chemokine signalling pathway so that we proposed Met and Dexa might affect its function in VSMCs. Based on the above descriptions, the aim of this study was to investigate the BARR2 gene and protein expression levels in VSMCs treated with Met and Dexa.…”

“…The work was followed on the results of FAK suppression in the Met‐treated VSMCs 19 . Similar to FAK (PTK2), BARR (ARRB), as an important central gene, was proposed to transduce the cellular signals from the upstream of chemokine signalling pathway (KEGG, hsa 04062).…”

“…VSMCs (National Cell Bank, Pasteur Institute, C591) were cultured in DMEM‐F12 containing FBS 10% (Gibco, Thermo Fisher Scientific‐US) and Pen‐strep 1% (Sigma‐Aldrich Co., St Louis, MO, USA) (5% CO2, 37°C). These cells were studied in 24 and 48‐h periods including: (A) Normal group, (B) High glucose (HG) group (25 mM), 13 , 19 (C) HG and Met groups (1 mM, 5 mM and 7 mM), 19 (D) HG and Dexa groups (10 −7 M, 10 −6 M and 10 −5 M). The VSMCs were exposed to Met and Dexa during the studied periods (24 and 48 h).…”

Role of advanced glycation end products on vascular smooth muscle cells under diabetic atherosclerosis

“…AGEs promote VSMCs migration by stimulating inflammatory cytokine production and activating multiple pathways, leading to arterial disease ( 161 , 162 ). Focal adhesion kinase (FAK) is expressed selectively in VSMCs, and links extracellular matrix/integrin and growth factors, inhibited FAK/PI3K/Akt pathways could promote VSMCs migration ( 185 , 186 ). It is suggested that RAGE silence by lentivirus transfection leads to reduce the phosphorylation of Akt, thus reducing the expression of migration-related proteins ( 187 ).…”