[Show abstract][Hide abstract] ABSTRACT: During several pathological processes such as cancer progression, thermal injury, wound healing and hindlimb ischemia, the mobilization of endothelial progenitor cells (EPCs) mobilization was enhanced with an increase of sympathetic nerve activity and norepinephrine (NE) secretion, yet the cellular and molecular mechanisms involved in the effects of NE on EPCs has less been investigated.
PLoS ONE 01/2014; 9(7):e101774. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidemiological and animal studies have suggested that chronic stress promotes tumourigenesis by promoting tumour angiogenesis. However, underlying mechanisms have not been fully elucidated. Endothelial progenitor cells (EPCs) are a group of bone marrow-derived cells that have an important function in neovascularisation of various tumour growths. In this study, chronic stress was hypothesised to increase tumour angiogenesis via sympathetic neurotransmitter-induced activation of EPCs through α1 adrenoreceptor (AR)-extracellular regulated protein kinases and β2 AR-endothelial nitric oxide synthase signal pathways. This hypothesis should be tested in several clinical and animal studies. Results may have implications on the development of new anti-tumour drugs.
[Show abstract][Hide abstract] ABSTRACT: Recent studies have demonstrated that palmitic acid (PA) could regulate endothelial progenitor cells (EPCs) function (migration, proliferation, survival and angiogenesis) via various signal pathways, but the effect of PA on EPCs apoptosis and associated mechanisms are still elusive.
The human EPCs were obtained by Ficoll density gradient centrifugation and cultured in M199 medium containing rh-VEGF (30ng/mL), rh-b-FGF (6ng/mL) and 10% fetal bovine serum for 7 days. The adhesive EPCs were harvested, then challenged with different concentrations of PA (ranging from 0 to 800mumol/L) for 48h and 400 micromol/L PA for different time periods (ranging from 0 to 60h) after 12h synchronization with serum-free medium. The EPCs apoptosis was determined by flow cytometry, expression of caspase-3, phosphorylated ERK1/2, JNK and p38 mitogen-activated protein kinase (MAPK) were quantified by Western blot. The effect of PA on caspase-3 activity in the absence or presence of specific MAPK pathway inhibitors was determined by colorimetry.
PA increased EPCs apoptosis in a dose- and time-dependent manner, upregulated phosphorylated-p38 and -JNK, caspase-3 expression of EPCs while ERK expression was not affected. PA-induced EPCs apoptosis could be partly ameliorated by p38 inhibitor SB203580 and JNK inhibitor SP600125, but not by ERK1/2 inhibitor PD98059.
These findings suggested that PA promoted EPCs apoptosis via p38 and JNK MAPKs pathways.
[Show abstract][Hide abstract] ABSTRACT: Advanced glycation end products (AGEs) and endothelial progenitor cells (EPCs) play key roles in pathogenesis of diabetes-related vascular complications. AGEs can induce dysfunction in EPCs. The peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists are widely used in the treatment of type 2 diabetes, and it remains unknown if they could attenuate EPC dysfunction induced by AGEs.
EPCs isolated from healthy adults were cultured with various concentrations of AGEs (0, 50, 100 and 200 mg L(-1)) with or without rosiglitazone (10 nM), antibody for the receptors for AGE-human serum albumin (anti-receptor for advanced glycation end products (RAGE); 50 microg mL(-1)), phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002, 5 microM), nitric oxide (NO) synthase inhibitor (L-N(G)-nitro-arginine methyl ester (L-NAME), 100 microM) or sodium nitroprusside (SNP, 25 microM). Proliferation, apoptosis, cell adhesion, migration and NO production in EPCs were assessed, and expressions of endothelial NO synthase (eNOS) and Akt were determined.
Number, proliferation/migration capacities, eNOS and Akt phosphorylation as well as NO synthesized by EPCs were increased by rosiglitazone and reduced by AGEs. AGEs promoted while rosiglitazone reduced EPC apoptosis. The AGE-induced effects were significantly ameliorated by pre-incubation with rosiglitazone, RAGE antibody and SNP. The beneficial effects of rosiglitazone could be blocked by pretreatment with L-NAME and LY294002.
The PPARgamma agonist rosiglitazone increased EPC function and attenuated EPC dysfunction induced by AGEs via upregulating the Akt-eNOS signal pathways of EPCs.
British Journal of Pharmacology 11/2009; 158(8):1865-73. · 5.07 Impact Factor