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J Appl Physiol (1985)
2016[Sep]; 121
(3
): 670-7
PMID27471237
show ga
Obstructive sleep apnea (OSA) is a common sleep disorder characterized by
intermittent hypoxia (IH). Clinical studies have previously shown that OSA is an
independent risk factor for atherosclerosis. Atherogenicity in OSA patients has
been assumed to be associated with the NF-?B pathways. Although foam cells are
considered to be a hallmark of atherosclerosis, how IH as in OSA affects their
development has not been fully understood. Therefore, we hypothesized that IH
induces macrophage foam cell formation through NF-?B pathway activation. To test
this hypothesis, peritoneal macrophages collected from myeloid-restricted
IKK-?-deleted mice were incubated with native LDL and exposed to either IH or
normoxia. After exposure, NF-?B pathway activity and intracellular cholesterol
were measured. In control macrophages, IH significantly increased NF-?B pathway
activity by 93% compared with normoxia (P < 0.05). However, such response to IH
was diminished by IKK-? deletion (increased by +31% compared with normoxia; P =
0.64), suggesting that IKK-? is critical for IH-induced NF-?B pathway activation.
Likewise, in control macrophages, total cholesterol was increased in IH compared
with normoxia (65.7 ± 3.8 ?g/mg cellular protein and 53.2 ± 1.2, respectively; P
< 0.05). However, this IH-induced foam cell formation was disappeared when IKK-?
was deleted (52.2 ± 1.2 ?g/mg cellular protein for IH and 46.3 ± 1.7 for
normoxia; P = 0.55). This IH-mediated effect still existed in macrophages without
LDL receptor. Taken together, our findings show that IH activates the
IKK-?-dependent NF-?B pathway and that this, in turn, induces foam cell formation
in murine macrophages.
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