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New insights into the roles of olfactory receptors in cardiovascular disease

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Abstract

Olfactory receptors (ORs) are G protein coupled receptors (GPCRs) with seven transmembrane domains that bind to specific exogenous chemical ligands and transduce intracellular signals. They constitute the largest gene family in the human genome. They are expressed in the epithelial cells of the olfactory organs and in the non-olfactory tissues such as the liver, kidney, heart, lung, pancreas, intestines, muscle, testis, placenta, cerebral cortex, and skin. They play important roles in the normal physiological and pathophysiological mechanisms. Recent evidence has highlighted a close association between ORs and several metabolic diseases. Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality globally. Furthermore, ORs play an essential role in the development and functional regulation of the cardiovascular system and are implicated in the pathophysiological mechanisms of CVDs, including atherosclerosis (AS), heart failure (HF), aneurysms, and hypertension (HTN). This review describes the specific mechanistic roles of ORs in the CVDs, and highlights the future clinical application prospects of ORs in the diagnosis, treatment, and prevention of the CVDs.

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In summary, ORs are widely expressed in multiple tissues of the body, and play various pathophysiological roles through different signaling pathways.

Abbreviations

OR51E1:

Olfactory Receptor Family 51 Subfamily E Member 1

Olfr2:

Olfactory receptor 2

OR2L13:

Olfactory Receptor Family 2 Subfamily L Member 13

Olfr78:

Olfactory receptor 78

OR1A1:

Olfactory Receptor Family 1 Subfamily A Member 1

Olfr544:

Olfactory receptor 544

OR1G1:

Olfactory Receptor Family 1 Subfamily G Member 1

OR51E2:

Olfactory Receptor Family 51 Subfamily E Member 2

MOR23:

Mouse olfactory receptor 23

MCFAS:

Medium-chain fatty acids

Gβγ:

G protein βγ subunits

PI3Kγ:

Phosphoinositide 3-kinase

IL-1β:

Interleukin-1β

NLRP3:

NOD-like receptor protein 3

cAMP:

Cyclic adenosine monophosphate

PKA:

Protein kinase A

CREB:

CAMP-response element binding protein

SCFAs:

Short-chain fatty acids

BP:

Blood pressure

RAAS:

Renin-angiotensin-aldosterone system

MCP-1:

Monocyte chemotactic protein-1

HES-1:

Hairy and enhancer of split-1

PPAR-γ:

Peroxisome proliferators-activated receptor-γ

GLUTag cells:

A mouse intestinal L cell line

GLP-1:

Glucagon-like peptide-1

p38 MAPK:

P38 mitogen-activated protein kinase

JNK:

C-Jun NH2-terminal kinase

SAPK:

Stress-activated protein kinases

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Funding

This study was funded by the National Natural Science Foundation of China (81870548, 81570721, 81500351); the Youth Medical Talent Project of Jiangsu Province (QNRC2016842); the open project of clinical medical research center of Gynecology and Traditional Chinese Medicine of Zhenjiang (SS202204-KFB05); the Science and Technology Commission of Zhenjiang City (FZ2020038); Clinical Medical Science and Technology Development Foundation of Jiangsu University (JLY2021209); Key project for Medical Education Collaborative Innovation Fund of Jiangsu University (JDY2022005) and Doctoral Research Initiation Fund (jdfyRC2020010).

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JJ and GY conceived and designed the review. KS and YJ wrote the original draft of the manuscript and made the figure. JJ and LY revised the final manuscript. All authors read and approved the final manuscript.

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Correspondence to Guoyue Yuan or Jue Jia.

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Shi, K., Jiao, Y., Yang, L. et al. New insights into the roles of olfactory receptors in cardiovascular disease. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-05024-x

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