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Therapeutic Targeting of the Carotid Body for Treating Sleep Apnea in a Pre-clinical Mouse Model.
Adv Exp Med Biol. 2018; 1071:109-114.AE

Abstract

Sleep apnea with periodic cessation of breathing during sleep is a highly prevalent respiratory disorder affecting an estimated 10% of adults. Patients with sleep apnea exhibit several co-morbidities including hypertension, stroke, disrupted sleep, and neurocognitive and metabolic complications. Emerging evidence suggests that a hyperactive carotid body (CB) chemo reflex is an important driver of apneas in sleep apnea patients. Gasotransmitters carbon monoxide (CO) and hydrogen sulfide (H2S) play important roles in oxygen sensing by the CB. We tested the hypothesis that an augmented CB chemo reflex stemming from disrupted CO-H2S signaling may lead to sleep apnea. This possibility was tested in mice deficient in hemeoxygenase-2 (HO-2), an enzyme involved in CO synthesis, which were shown to exhibit hyperactive CB activity due to high H2S levels. We found that HO-2-/- mice exhibit a high incidence of apneas during sleep compared to wild type mice. Blocking the CB hyperactivity with L-propargylglycine, an inhibitor of cystathionine-γ-lyase (CSE), which catalyzes H2S synthesis, prevented apneas in HO-2-/- mice. These findings suggest that targeting CB with inhibitors of CSE might be a novel therapeutic strategy for preventing sleep apnea.

Authors+Show Affiliations

Institute for Integrative Physiology and Center for Systems Biology of Oxygen Sensing, Biological Sciences Division, University of Chicago, Chicago, IL, USA.Institute for Integrative Physiology and Center for Systems Biology of Oxygen Sensing, Biological Sciences Division, University of Chicago, Chicago, IL, USA.Institute for Integrative Physiology and Center for Systems Biology of Oxygen Sensing, Biological Sciences Division, University of Chicago, Chicago, IL, USA.Institute for Integrative Physiology and Center for Systems Biology of Oxygen Sensing, Biological Sciences Division, University of Chicago, Chicago, IL, USA. nanduri@uchicago.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30357741

Citation

Peng, Ying-Jie, et al. "Therapeutic Targeting of the Carotid Body for Treating Sleep Apnea in a Pre-clinical Mouse Model." Advances in Experimental Medicine and Biology, vol. 1071, 2018, pp. 109-114.
Peng YJ, Zhang X, Nanduri J, et al. Therapeutic Targeting of the Carotid Body for Treating Sleep Apnea in a Pre-clinical Mouse Model. Adv Exp Med Biol. 2018;1071:109-114.
Peng, Y. J., Zhang, X., Nanduri, J., & Prabhakar, N. R. (2018). Therapeutic Targeting of the Carotid Body for Treating Sleep Apnea in a Pre-clinical Mouse Model. Advances in Experimental Medicine and Biology, 1071, 109-114. https://doi.org/10.1007/978-3-319-91137-3_14
Peng YJ, et al. Therapeutic Targeting of the Carotid Body for Treating Sleep Apnea in a Pre-clinical Mouse Model. Adv Exp Med Biol. 2018;1071:109-114. PubMed PMID: 30357741.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic Targeting of the Carotid Body for Treating Sleep Apnea in a Pre-clinical Mouse Model. AU - Peng,Ying-Jie, AU - Zhang,Xiuli, AU - Nanduri,Jayasri, AU - Prabhakar,Nanduri R, PY - 2018/10/26/entrez PY - 2018/10/26/pubmed PY - 2019/7/19/medline KW - Carbon monoxide KW - Central sleep apnea KW - Cystathionine-γ-lyase KW - Hemeoxygenase-2 KW - Hydrogen sulfide KW - Obstructive SP - 109 EP - 114 JF - Advances in experimental medicine and biology JO - Adv Exp Med Biol VL - 1071 N2 - Sleep apnea with periodic cessation of breathing during sleep is a highly prevalent respiratory disorder affecting an estimated 10% of adults. Patients with sleep apnea exhibit several co-morbidities including hypertension, stroke, disrupted sleep, and neurocognitive and metabolic complications. Emerging evidence suggests that a hyperactive carotid body (CB) chemo reflex is an important driver of apneas in sleep apnea patients. Gasotransmitters carbon monoxide (CO) and hydrogen sulfide (H2S) play important roles in oxygen sensing by the CB. We tested the hypothesis that an augmented CB chemo reflex stemming from disrupted CO-H2S signaling may lead to sleep apnea. This possibility was tested in mice deficient in hemeoxygenase-2 (HO-2), an enzyme involved in CO synthesis, which were shown to exhibit hyperactive CB activity due to high H2S levels. We found that HO-2-/- mice exhibit a high incidence of apneas during sleep compared to wild type mice. Blocking the CB hyperactivity with L-propargylglycine, an inhibitor of cystathionine-γ-lyase (CSE), which catalyzes H2S synthesis, prevented apneas in HO-2-/- mice. These findings suggest that targeting CB with inhibitors of CSE might be a novel therapeutic strategy for preventing sleep apnea. SN - 0065-2598 UR - https://www.unboundmedicine.com/medline/citation/30357741/Therapeutic_Targeting_of_the_Carotid_Body_for_Treating_Sleep_Apnea_in_a_Pre_clinical_Mouse_Model_ L2 - https://dx.doi.org/10.1007/978-3-319-91137-3_14 DB - PRIME DP - Unbound Medicine ER -