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Vascular macrophages sense octanal and drive athero-inflammation

Cellular & Molecular Immunology volume 19, pages 1077–1078 (2022)Cite this article

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Atherosclerosis is recognized as a chronic inflammatory disease characterized by the deposition of modified lipids and the infiltration of macrophages in the arterial vasculature. Macrophages play essential roles in the immune-inflammatory responses in atherosclerotic plaques by taking up cholesterol and producing various cytokines. Among these cytokines, the interleukin (IL)-1 family cytokines, particularly IL-1β, have multiple effects on the cardiovascular system. The IL-1β precursor undergoes proteolytic cleavage by caspase-1 to produce a mature form that possesses biological activity. Caspase-1 in turn undergoes activation by a supramolecular assembly known as the inflammasome, of which the NLRP3 inflammasome is the most important because it is activated by a large variety of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) [2]. Thus, the NLRP3 inflammasome/IL-1β axis serves as an important vascular and systemic inflammatory mediator that contributes to atherogenesis. In 2017, the results of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) trial demonstrated that reducing inflammation in cardiovascular disease patients by neutralizing IL-1β with canakinumab decreased the risk of developing cardiovascular events [3]. However, systemically targeting inflammatory pathways might disturb immune homeostasis and cause opportunistic infections. Nevertheless, the success of CANTOS will prompt more studies to evaluate other measures of manipulating inflammation in atherosclerosis.

OLFRs are a large family of G protein-coupled receptors, and there are ~1100 functional genes in mice and 400 in humans. Most OLFRs are expressed in the olfactory epithelium of the nose and play essential roles in the detection of environmental odors and pheromones. However, OLFRs are also found in sperm, testes, skin, pancreatic islets and the intestine, suggesting that these receptors can do more than just recognize smell, such as sperm chemotaxis, renin secretion, metabolism and tissue repair. Over the past 2 years, scientists at the La Jolla Institute for Immunology have unexpectedly found the expression of OLFRs and their downstream signaling components in vascular macrophages isolated from the atherosclerotic aortas of mice [4], but the role of OLFRs in atherosclerosis remains unclear.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81970373, 31770977 and 81920108003), the Postdoctoral Science Foundation of China and Shandong Province (No. 2018M630789 and No. 201901009), the Shandong Provincial Natural Science Foundation (ZR2020YQ53), the National Key Research and Development Program of China (2021YFF0501403), the Taishan Scholars Program of Shandong Province (ZM and ZC), and the Fundamental Research Funds for the Central Universities (No. 2018JC001).

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  1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

    Lei Qiao, Meng Zhang & Cheng Zhang

  2. Cardiovascular Disease Research Center of Shandong First Medical University, Central Hospital Affiliated to Shandong First Medical University, Jinan, China

    Meng Zhang & Cheng Zhang

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  1. Lei Qiao
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Correspondence to Meng Zhang or Cheng Zhang.

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Qiao, L., Zhang, M. & Zhang, C. Vascular macrophages sense octanal and drive athero-inflammation. Cell Mol Immunol 19, 1077–1078 (2022). https://doi.org/10.1038/s41423-022-00896-9

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