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Transcriptome of SHR Carotid Bodies Reveals Novel Peptide Receptors Associated with Hypertension
Author(s) -
Pauza Audrys G.,
Paton Julian,
Murphy David
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09809
Subject(s) - carotid body , transcriptome , receptor , medicine , stimulus (psychology) , phenotype , biology , bioinformatics , endocrinology , gene , stimulation , genetics , gene expression , psychology , psychotherapist
Background The epidemic of hypertension demands novel therapeutic strategies and innovative multi‐system approach to clinical management. The carotid body (CB) is the primary site of peripheral chemoreception in the human body. CB dysfunction has been implicated in numerous cardio‐respiratory and metabolic conditions, including essential hypertension, diabetes mellitus, sleep apnoea and heart failure. Recent attempts to modulate CB activity has proven successful in alleviating symptoms despite lacking specificity at the target organ. The ribbon‐cable hypothesis suggests that the CB is composed of specialised chemosensory subunits responsive to a specific stimulus in the bloodstream 1. Aim We hypothesised that the hypertensive phenotype is associated with alterations in a subset of chemosensory subunits, identification of which would offer highly specific therapeutic opportunities for clinical intervention. Methods We performed a high‐throughput transcriptomic screen of the CBs in the spontaneously hypertensive (SHR) and the normotensive Wistar‐Kyoto (WKY) rats. Results Transcriptomic screen of the SHR CBs revealed numerous differentially expressed genes associated with the hypertensive state. Our experimental design uncovered underlying lateral differences between the CBs at the intra‐individual level. Network analysis revealed genes associated with serine metabolism, oxidoreductase activity, and G protein‐coupled receptors to be significantly enriched in the WKY‐SHR comparison. A number of previously unidentified peptide receptors were found to be differentially expressed in the SHR. Conclusion Newly identified receptors serve as candidate genes for pre‐clinical proof of concept and feasibility functional studies. This provides a unique opportunity to design novel therapies to abate carotid body tonicity and hyperreflexia in neurogenic and metabolic hypertension. Support or Funding Information This work has been generously supported by the British Heart Foundation (BHF)1 Zera et al. ( 2019 ) Physiology 34 : 4 , 264 – 282 ; PubMed: 31165684