The human carotid body transcriptome with focus on oxygen sensing and inflammation – a comparative analysis

Abstract

Key points• The carotid body (CB) is the key oxygen sensor and governs the ventilatory response to hypoxia.• CB oxygen sensing and signalling gene expression is well described in animals whereas human data are absent.• Here we have characterized the human CB global gene expression in comparison with functionally related tissues and mouse CB gene expression.• We show that the human CB expresses oxygen sensing genes in common with mice but also differs on key genes such as certain K + channels. There is moreover increased expression of inflammatory response genes in human and mouse CBs in comparison with related tissues.• The study establishes similarities but also important differences between animal and human CB gene expression profiles and provides a platform for future functional studies on human CBs.Abstract The carotid body (CB) is the key oxygen sensing organ. While the expression of CB specific genes is relatively well studied in animals, corresponding data for the human CB are missing. In this study we used five surgically removed human CBs to characterize the CB transcriptome with microarray and PCR analyses, and compared the results with mice data. In silico approaches demonstrated a unique gene expression profile of the human and mouse CB transcriptomes and an unexpected upregulation of both human and mouse CB genes involved in the inflammatory response compared to brain and adrenal gland data. Human CBs express most of the genes previously proposed to be involved in oxygen sensing and signalling based on animal studies, including NOX2, AMPK, CSE and oxygen sensitive K + channels. In the TASK subfamily of K + channels, TASK-1 is expressed in human CBs, while TASK-3 and TASK-5 are absent, although we demonstrated both TASK-1 and TASK-3 in one of the mouse reference strains. Maxi-K was expressed exclusively as the spliced variant ZERO in the human CB. In summary, the human CB transcriptome shares important features with the mouse CB, but also differs significantly in the expression of a number of CB chemosensory genes. This study provides key information for future functional investigations on the human carotid body.

GAL-021 and GAL-160 are Efficacious in Rat Models of Obstructive and Central Sleep Apnea and Inhibit BKCa in Isolated Rat Carotid Body Glomus Cells

“…In the rat carotid body much evidence points to the presence and functional importance of BKCa and TASK channels in chemotransduction (Buckler, 2007;Peers et al, 2010;Kim et al, 2012). There are few reports relating to human carotid body chemotranduction, although a recent report documents that the human carotid body transcriptome contains BKCa and TASK-1 channels (Mkrtchian et al, 2012). To probe further the site and mechanism of action of GAL-021 and GAL-160, we compared the evoked ventilatory stimulation in rats subjected to acute bilateral carotid sinus nerve transection or sham surgery.…”

Chronic Caffeine Intake in Adult Rat Inhibits Carotid Body Sensitization Produced by Chronic Sustained Hypoxia but Maintains Intact Chemoreflex Output

“…Thus, acclimatization is of prime importance to minimize hypoxia. Chronic hypoxia modifies CB gene expression (Huey and Powell, 2000;Ganfornina et al, 2005;Caceres et al, 2007;Mkrtchian et al, 2012), causes hypertrophy of chemoreceptor cells, a proliferation and widening of organ capillaries (Laidler and Kay, 1975), and also modifies neurotransmitter dynamics at the CBs [including dopamine (DA), acetylcholine (ACh), and ATP] (Powell, 2007). Yet, the mechanisms of acclimatization remain elusive.…”

Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body

“…Several papers have also described the systemic cardio-respiratory alterations caused by bilateral CB resection (Timmers et al 2003 ) or ageing (Di Giulio et al 2012 ;Pokorski et al 2004 ) in humans. However, with the exception of two recent publications on the gene expression profi le of the human CB (Fagerlund et al 2010 ;Mkrtchian et al 2012 ), its functional characteristics have remained practically unknown. Herein we summarize and discuss the data recently obtained by our group regarding the basic anatomical, neurochemical and physiological properties of CBs dissected from human cadavers, of different age and gender, registered with the Organ Donation Program at our institution (Ortega-Saenz et al 2013 ).…”