Endothelial Progenitor Cells in Acute Myocardial Infarction and Sleep-disordered Breathing

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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 vitroon 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 IHin vitrowere 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 IHin vitrocompared 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. IHin vitrohad similar effects on healthy EPC functions.

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