Intermittent hypoxia: Friend or foe on endothelial repair in mouse model

Abstract

Aim of the study: Obstructive sleep apnea, which is characterized by intermittent hypoxia (IH), is a common respiratory disease. The aim of the present study was to explore the relationship between hypoxia and endothelial progenitor cell (EPC) function, and explain the role of IH in endothelial repair. Materials and methods: Peripheral blood mononuclear cells (PBMCs) were isolated from a mouse model of IH. The number of CD133 þ kinase insert domain receptor (KDR) þ , CD133 þ CD34 þ , CD34 þ KDR þ and ALDH low CD34 þ KDR þ EPCs was determined by flow cytometry. HIF-1a, stromal-derived factor-1 (SDF-1) a and VEGF were measured by ELISA. The proliferative ability of PBMCs was determined. EPC migration was assessed by Transwell assay and surface proteins by western blot analysis. EPCs were co-cultured with mouse brain endothelial cells and their angiogenic ability was analyzed. Results: The number of CD133 þ KDR þ , CD133 þ CD34 þ and CD34 þ KDR þ EPCs increased with IH ingravescence. The number of ALDH low CD34 þ KDR þ EPCs with mild IH stimulation was higher and gradually decreased in the moderate and severe IH groups. The release of HIF-1a, SDF-1a and VEGF in the serum increased with the increase in the degree of IH. In the mild IH treatment, the migration and angiogenesis of EPCs, as well as the expression of vascular endothelial growth factor receptor 2 and cysteine-X-cysteine receptor 4, were higher than those in the control group, but progressively decreased in the groups with moderate and severe IH. Conclusion: Increased levels of IH accelerated the increase in vasoactive factors in peripheral blood, thereby mobilizing a large number of EPCs. Increasing of IH diminished the mobilization, chemotactic and angiogenetic ability of EPCs.

Determination of the autophagic flux in murine and human peripheral blood mononuclear cells

“…Regarding the literature different density gradients were applied for PBMC isolation. For instance, PBMC isolation was published using 1.077 g/cm³ in C57BL/6 mice ( Mendez-David et al, 2013 ; Song et al, 2021 ), whereas 1.084 g/cm³ was used for MRL(-Ipr) mice ( Wang et al, 2018 ). Based on the literature, we tried for murine PBMC isolation a Percoll solution with 1.080 g/cm³ ( Mizobe et al, 1982 ) and compared this to Ficoll™-Plaque PLUS with 1.077 g/cm³.…”

Severe Intermittent Hypoxia Modulates the Macrophage Phenotype and Impairs Wound Healing Through Downregulation of HIF-2α

“…Another study also revealed that moderate and severe intermittent hypoxia diminished the mobilization, chemotactic and angiogenetic ability of endothelial progenitor cells. 44 Chronic severe intermittent hypoxia-induced mitochondrial dysfunction could mediate endothelial oxidative stress and apoptosis. 45 , 46 Re-epithelization involving keratinocytes and angiogenesis involving vascular endothelial cells are critical to wound healing.…”