Repetitive hypoxia increases lipid loading in human macrophages-a potentially atherogenic effect.
Obstructive sleep apnea (OSA) is characterized by repetitive episodes of hypoxia and is associated with an increase in cardiovascular disease. We, therefore, investigated the effect of repetitive hypoxia on two key early events in atherogenesis; lipid loading in foam cells and monocyte adhesion to endothelial cells. Human macrophages were loaded with acetylated low-density lipoproteins. During lipid loading, the cells were exposed to 30 min cycles of 2%/21% oxygen or control (room air, 5% CO(2) incubator). Human umbilical vein endothelial cells (HUVECs) were also exposed to 30 min cycles of repetitive hypoxia or control conditions and monocyte adhesion measured. Cell adhesion molecules E-selectin, ICAM-1 and VCAM-1 were measured by ELISA. Repetitive hypoxia increased cholesteryl ester uptake by macrophages (127+/-5% compared to controls; p=0.003). By contrast, monocyte adhesion to HUVECs and cell adhesion molecule expression were unchanged by exposure to repetitive hypoxia, compared to controls (p >0.1). Repetitive hypoxia, at levels relevant to tissues such as the arterial wall, enhances lipid uptake into human macrophages. This may contribute to accelerated atherosclerosis in OSA patients.
Lattimore
Jo-Dee L
JD
Department of Cardiology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW 2050, Australia. jodee.lattimore@email.cs.nsw.gov.au
Wilcox
Ian
I
Nakhla
Shirley
S
Langenfeld
Matthias
M
Jessup
Wendy
W
Celermajer
David S
DS
D001161:Arteriosclerosis / Q000503:physiopathology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D042783:Endothelial Cells; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D050356:Lipid Metabolism; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000502:physiology; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000150:complications*
D015815:Cell Adhesion Molecules