Slava Berger1, Doron Aronson, Peretz Lavie, Lena Lavie. 1. The Lloyd Rigler Sleep Apnea Research Laboratory, Unit of Anatomy and Cell Biology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Abstract
RATIONALE: Mobilization and functions of endothelial progenitor cells (EPCs) are increased in patients with acute myocardial infarction (AMI). Yet, sleep-disordered breathing (SDB) is highly prevalent in patients with AMI. OBJECTIVES: To compare EPC numbers and functions in patients with AMI with SDB (AMI-SDB) and without SDB (AMI-only) and to determine the effects of intermittent hypoxia (IH) in vitro on EPC proliferative and angiogenic properties. METHODS: Forty male patients with AMI underwent a whole-night sleep study using ambulatory monitoring. Nineteen had SDB (oxygen desaturation index > 5 events/h). AMI-SDB and AMI-only patients were matched by age, body mass index, blood chemistry, and comorbidities. Blood samples were analyzed by flow cytometry, endothelial cell colony-forming units (EC-CFU), paracrine measures, blood chemistry, and oxidative stress, inflammatory, and angiogenic markers. Effects of IH in vitro were studied in 12 healthy subjects. MEASUREMENTS AND MAIN RESULTS: Circulating EPCs (CD34(+)/KDR(+)), angiogenic T cells (CD3(+)/CD31(+)/CXCR4(+)), and vascular endothelial growth factor in monocytes were significantly higher in AMI-SDB patients, whereas plasma stromal cell-derived factor (SDF)-1α levels were significantly lower. Also, EC-CFU numbers and EC-CFU paracrine effects on endothelial tube formation were significantly higher in AMI-SDB compared with AMI-only patients. Similarly, in cell cultures from healthy subjects, EC-CFU numbers and their paracrine effects on endothelial tube formation were increased after exposure to IH in vitro compared with normoxia. CONCLUSIONS: Coexistent mild to moderate SDB in patients with AMI increased the mobilization, proliferative and angiogenic capacities of EPCs, angiogenic T-cell numbers, and vascular endothelial growth factor expression in monocytes compared with patients with AMI without SDB. IH in vitro had similar effects on healthy EPC functions.
RATIONALE: Mobilization and functions of endothelial progenitor cells (EPCs) are increased in patients with acute myocardial infarction (AMI). Yet, sleep-disordered breathing (SDB) is highly prevalent in patients with AMI. OBJECTIVES: To compare EPC numbers and functions in patients with AMI with SDB (AMI-SDB) and without SDB (AMI-only) and to determine the effects of intermittent hypoxia (IH) in vitro on EPC proliferative and angiogenic properties. METHODS: Forty male patients with AMI underwent a whole-night sleep study using ambulatory monitoring. Nineteen had SDB (oxygen desaturation index > 5 events/h). AMI-SDB and AMI-only patients were matched by age, body mass index, blood chemistry, and comorbidities. Blood samples were analyzed by flow cytometry, endothelial cell colony-forming units (EC-CFU), paracrine measures, blood chemistry, and oxidative stress, inflammatory, and angiogenic markers. Effects of IH in vitro were studied in 12 healthy subjects. MEASUREMENTS AND MAIN RESULTS: Circulating EPCs (CD34(+)/KDR(+)), angiogenic T cells (CD3(+)/CD31(+)/CXCR4(+)), and vascular endothelial growth factor in monocytes were significantly higher in AMI-SDBpatients, whereas plasma stromal cell-derived factor (SDF)-1α levels were significantly lower. Also, EC-CFU numbers and EC-CFU paracrine effects on endothelial tube formation were significantly higher in AMI-SDB compared with AMI-only patients. Similarly, in cell cultures from healthy subjects, EC-CFU numbers and their paracrine effects on endothelial tube formation were increased after exposure to IH in vitro compared with normoxia. CONCLUSIONS: Coexistent mild to moderate SDB in patients with AMI increased the mobilization, proliferative and angiogenic capacities of EPCs, angiogenic T-cell numbers, and vascular endothelial growth factor expression in monocytes compared with patients with AMI without SDB. IH in vitro had similar effects on healthy EPC functions.
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