Intermittent Hypoxia and Hypercapnia Induces Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Beta-dependent Atherosclerosis in Pulmonary Arteries.
Intermittent Hypoxia and Hypercapnia Induces Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Beta-dependent Atherosclerosis in Pulmonary Arteries.
Am J Physiol Regul Integr Comp Physiol. 2019 Oct 16;:
Authors: Imamura T, Xue J, Poulsen O, Zhou D, Karin M, Haddad GG
Abstract
Clinical studies have shown that obstructive sleep apnea (OSA) increases atherosclerosis risk. The inflammation, especially mediated by the macrophages via nuclear factor-kappa B (NF-κB), has been speculated to contribute to atherogenicity in OSA patients. Inhibitor of NF-κB kinase subunit beta (IKKβ) is an essential element of NF-κB pathway and is linked to atherosclerosis. We previously reported that atherosclerosis was accelerated in pulmonary artery (PA) but not in aorta when low-density lipoprotein receptor knockout (Ldlr-/-) mice were exposed to intermittent hypoxia/hypercapnia (IHH), a surrogate for recurrent upper airway obstruction. Therefore, we hypothesized that IKKβ-dependent NF-κB activation in monocytes and macrophages plays a role in IHH-induced PA atherosclerosis. To test this hypothesis, myeloid restricted IKKβ deletion (IkkβΔMye) or control (IkkβF/F) mice were crossed to Ldlr-/- mice to generate double knockout mice. Then the mice were exposed to IHH or Air on high fat diet for 8 or 16 weeks. Lesions of PA and aorta were examined in IkkβΔMye-Ldlr-/-and IkkβF/F-Ldlr-/- male mice, under IHH versus Air. The results revealed that IKKÎ...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Imamura T, Xue J, Poulsen O, Zhou D, Karin M, Haddad GG Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research
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