| First Author | Imamura T | Year | 2019 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 317 |
| Issue | 6 | Pages | R763-R769 |
| PubMed ID | 31618063 | Mgi Jnum | J:282222 |
| Mgi Id | MGI:6379933 | Doi | 10.1152/ajpregu.00056.2019 |
| Citation | Imamura T, et al. (2019) Intermittent hypoxia and hypercapnia induces inhibitor of nuclear factor-kappaB kinase subunit beta-dependent atherosclerosis in pulmonary arteries. Am J Physiol Regul Integr Comp Physiol 317(6):R763-R769 |
| abstractText | Clinical studies have shown that obstructive sleep apnea (OSA) increases atherosclerosis risk. The inflammation, especially mediated by the macrophages via nuclear factor-kappaB (NF-kappaB), has been speculated to contribute to atherogenicity in OSA patients. Inhibitor of NF-kappaB kinase-beta (IKKbeta) is an essential element of the NF-kappaB 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 IKKbeta-dependent NF-kappaB activation in monocytes and macrophages plays a role in IHH-induced PA atherosclerosis. To test this hypothesis, myeloid restricted IKKbeta deletion (Ikkbeta(DeltaMye)) or control (Ikkbeta(F/F)) mice were crossed with Ldlr(-/-) mice to generate double-knockout mice. Then, the mice were exposed to IHH or room air (Air) on high-fat diet for 8 or 16 wk. Lesions of PA and aorta were examined in Ikkbeta(DeltaMye);Ldlr(-/-) and Ikkbeta(F/F);Ldlr(-/-) male mice under IHH vs. Air. The results revealed that IKKbeta deletion abolished IHH-induced PA atherosclerosis after 8-wk exposure but not after 16-wk exposure (8 wk: Ikkbeta(F/F);Ldlr(-/-), IHH 13.5 +/- 1.4 vs. Air 5.7 +/- 0.7%, P < 0.01; Ikkbeta(DeltaMye);Ldlr(-/-), IHH 7.4 +/- 1.9% vs. Air 4.6 +/- 1.3%, P = 0.24). Both IKKbeta deletion and IHH had no effects on atherosclerosis in the aorta. Our findings demonstrate that IKKbeta-dependent NF-kappaB activity in myeloid-lineage cells plays a critical role in IHH-induced PA atherosclerosis at the early stage. |
