Hypoxia-inducible factor-1: a molecular hint of physiological changes in the carotid body during long-term hypoxemia?
The aims of this review are to describe recent data focusing on the anatomical, functional and molecular changes of the carotid body during chronic hypoxemia, and to summarize current views in the literature relevant to the topic. The carotid body is the major peripheral sensor for detecting chemicals in the arterial blood. In acute hypoxia, carotid chemoreceptors transduce the signal to the brain for triggering reflexive responses of the cardiopulmonary system. The carotid body enlarges and changes its hypoxic sensitivity in humans and animals living at high altitude or subject to long-term hypoxemia associated with chronic cardiopulmonary diseases or hematological disorders. Recently, a surge of new evidence suggests that a heterodimeric transcriptional factor directly induced by severe tissue or cellular hypoxia, namely hypoxia-inducible factor-1 (HIF-1), is a key controller for the transcriptional regulation of the gene expression of a spectrum of proteins for the cellular response to hypoxia. These proteins, such as endothelin-1, type II nitric oxide synthase and vascular endothelial growth factor, play important physiological roles in the control of vascular tone and angiogenesis. In the carotid body, chronic hypoxemia induces remodeling of the vasculature, stimulates proliferation of the chemosensitive cells, and changes their excitability and sensitivity to chemical signals. In addition, HIF-1-targeted genes are expressed in the carotid body and the expression is modulated by chronic hypoxemia, suggesting an active role for HIF-1 in moderate levels of hypoxic stress.
Fung
Man-Lung
ML
Department of Physiology and Institute of Cardiovascular Science and Medicine, Faculty of Medicine, University of Hong Kong, Hong Kong, China. fungml@hkucc.hku.hk
D000818:Animals; D002344:Carotid Body / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000378:metabolism*; D017466:Receptors, Endothelin / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D004268:DNA-Binding Proteins; D019332:Endothelin-1; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D017466:Receptors, Endothelin; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D040262:Receptors, Vascular Endothelial Growth Factor