Platelets in angiogenesis and pulmonary progenitor cell homing under chronic intermittent hypoxia.

Platelets play a critical role in tissue repair and contain various molecules that regulate angiogenesis, such as stromal cell-derived factor-1 (SDF-1) which stimulates endothelial progenitor cells (EPCs). Chronic intermittent hypoxia (CIH) alters platelet function, but its specific impact on platelet-derived angiogenic factors and endothelial progenitor cell (EPC) recruitment in lung injury remains unclear. This study investigated the effects of CIH on the profile of pro- and anti-angiogenic molecules in platelets and their role in EPC homing during acute lung injury (ALI). Ten-week-old 35 rats were divided into control, ALI, CIH and CIH + ALI groups. CIH was applied for 6 h per day over 42 days, simulating an altitude of 3,000 m., approximately 14% O2. Blood and lung samples were taken three days after ALI. Vascular endothelial growth factor (VEGF), SDF-1, platelet-derived growth factor (PDGF), endostatin, thrombospondin-1, and plasminogen activator inhibitor-1 (PAI-1) were measured in platelet specimens. EPC homing to the lung was assessed via immunofluorescence for VEGFR2 and CD133. The CIH + ALI group exhibited a significant increase in platelet count. However, concentrations of SDF-1, VEGF, PDGF, PAI-1, endostatin, and thrombospondin-1 per platelet were significantly lower in this group. While EPC homing was prominent in the ALI group, it was absent in both CIH and CIH + ALI groups. These findings demonstrate that CIH reprograms the angiogenic cargo of platelets, characterized by a specific reduction in SDF-1 and a general dilution of other factors. This altered platelet profile, coupled with the absence of EPC recruitment, suggests a novel mechanism by which CIH may impair vascular repair in the injured lung via decreased platelet-derived SDF-1.