PPAR‐γ agonist pioglitazone prevents apoptosis of endothelial progenitor cells from rat bone marrow

Abstract

Selective peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist affects the functions of endothelial progenitor cells (EPCs). This study explores the effect of selective PPAR-γ agonist, pioglitazone, on EPC apoptosis. The cells were cultured and identified via the double staining method in a medium containing different concentrations of pioglitazone. EPC apoptosis was detected by flow cytometry. On Day 7, EPCs engulfed DiL-ac-LDL and FITC-UEA-1, and showed yellow fluorescence in a laser-scanning confocal microscope. EPC apoptosis inhibition was maximal at 50 µmol/L. The ability of pioglitazone to prevent EPC apoptosis may be mediated by the PI3K/Akt signal pathway. The use of thiazolidine two ketone (TZD) to reduce EPC apoptosis may have some potential in treating vascular diseases.

Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress

“…The positive effect of TZDs on CSC survival with exposure to oxidative agents is consistent with previous studies using other stem cell types [6, 10, 33, 34]. Rosiglitazone treatment protected neuroblasts against apoptosis via upregulation of Bcl-2/Bcl-xl and maintenance of mitochondrial membrane potential under increased H 2 O 2 production induced by hypoxia-reperfusion [33].…”

“…Rosiglitazone treatment protected neuroblasts against apoptosis via upregulation of Bcl-2/Bcl-xl and maintenance of mitochondrial membrane potential under increased H 2 O 2 production induced by hypoxia-reperfusion [33]. In addition, both rosiglitazone and pioglitazone have demonstrated protection of EPCs against apoptosis under oxidative stress [10, 27, 34]. Also of note is that rosiglitazone and pioglitazone restored functional ability of endothelial progenitor cells from type II diabetics to participate in re-endothelialization [5, 23, 26].…”

“…The cytoprotective role of TZDs under oxidative stress appears to be independent of PPARγ signaling [10, 34]. Conversely, most of the data regarding the impact of TZDs on improvement in EPC function, particularly the studies involving in vivo interventions, have been documented as dependent on PPARγ activation and secondary rise in adiponectin expression [26, 29, 33].…”

PPAR Gamma and Angiogenesis: Endothelial Cells Perspective

“…These discrepancies are mainly due to the strong phenotypic overlap between EPCs and circulating proangiogenic cells from the hematopoietic lineage, a lack of universal data reporting, and—as reported before—differing definitions of the studied cell populations [11]. It was thought that EPCs are present in the bone marrow niche, from where, in response to injury or hypoxia, they are released into the blood and mobilized to the injured tissue [9, 12, 13]. It was originally postulated that, after entering a damaged or ischemic tissue, EPCs stimulate the formation of blood vessels by differentiating into mature endothelial cells (Figure 2).…”

Regulation of EPCs: The Gateway to Blood Vessel Formation

“…Supporting an anti-inflammatory role of PPAR , Verma and colleagues showed that C-reactive protein-dependent impairment of EPC number and function was ameliorated with rosiglitazone treatment [117]. Furthermore, H 2 O 2 − and TNF -induced apoptosis of EPCs have been shown to be inhibited by pioglitazone and rosiglitazone treatment, respectively [113,118,119]. Consistent with these findings, activation of PPAR has been shown to enhance EPC numbers.…”