Coleman, James L J and Mouat, Margaret A and Wu, Jianxin and Jancovski, Nikola and Bassi, Jaspreet K and Chan, Andrea Y and Humphreys, David T and Mrad, Nadine and Yu, Ze-Yan and Ngo, Tony and Iismaa, Siiri and Dos Remedios, Cristobal G and Feneley, Michael P and Allen, Andrew M and Graham, Robert M and Smith, Nicola J (2018) Orphan receptor GPR37L1 contributes to the sexual dimorphism of central cardiovascular control. Biology of Sex Differences, 9 (1). p. 14. ISSN 2042-6410 (OA)
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Abstract
BACKGROUND
Over 100 mammalian G protein-coupled receptors are yet to be matched with endogenous ligands; these so-called orphans are prospective drug targets for the treatment of disease. GPR37L1 is one such orphan, abundant in the brain and detectable as mRNA in the heart and kidney. GPR37L1 ablation was reported to cause hypertension and left ventricular hypertrophy, and thus, we sought to further define the role of GPR37L1 in blood pressure homeostasis.
METHODS
We investigated the cardiovascular effects of GPR37L1 using wild-type (GPR37L1) and null (GPR37L1) mice established on a C57BL/6J background, both under baseline conditions and during AngII infusion. We profiled GPR37L1 tissue expression, examining the endogenous receptor by immunoblotting and a β-galactosidase reporter mouse by immunohistochemistry.
RESULTS
GPR37L1 protein was abundant in the brain but not detectable in the heart and kidney. We measured blood pressure in GPR37L1and GPR37L1mice and found that deletion of GPR37L1 causes a female-specific increase in systolic, diastolic, and mean arterial pressures. When challenged with short-term AngII infusion, only male GPR37L1mice developed exacerbated left ventricular hypertrophy and evidence of heart failure, while the female GPR37L1mice were protected from cardiac fibrosis.
CONCLUSIONS
Despite its absence in the heart and kidney, GPR37L1 regulates baseline blood pressure in female mice and is crucial for cardiovascular compensatory responses in males. The expression of GPR37L1 in the brain, yet absence from peripheral cardiovascular tissues, suggests this orphan receptor is a hitherto unknown contributor to central cardiovascular control.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 09 Apr 2018 00:04 |
| Last Modified: | 24 Apr 2018 06:28 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/715 |
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