Olfactory receptor 2 activation in macrophages: novel mediator of atherosclerosis progression.
Olfactory receptor 2 activation in macrophages: novel mediator of atherosclerosis progression.
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巨噬细胞中嗅觉受体 2 的激活：动脉粥样硬化进展的新介质
DOI：
10.1038/s41392-022-01115-7
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发表时间：
2022-07-21
影响因子：
39.3
通讯作者：
Wang, Dao Wen
中科院分区：
文献类型：
--
作者：
He, Zuowen;Wang, Dao Wen
高胆固醇血症和高低密度脂蛋白（LDL）水平已被确定为动脉粥样硬化性心血管疾病（ASCVD）的主要危险因素，ASCVD是人类死亡的主要原因。降LDL治疗可有效降低ASCVD风险约30- 50%2，推荐用于一级和二级预防。然而，相当数量的ASCVD患者对降LDL治疗的反应较差;因此，识别和控制其他风险因素是降低ASCVD发病率的关键。嗅觉受体（ORs）属于一个结构多样的蛋白质家族，能够检测环境中的大量气味。在包括人类在内的脊椎动物中，OR通常位于嗅觉上皮中的感觉神经元的表面上。然而，OR也发生在嗅上皮外的组织中。Parmentier等人首先鉴定出在哺乳动物生殖细胞中的嗅上皮外表达的OR基因转录物。3随后的研究表明，OR也位于其他人体组织中，包括肺，睾丸，肠，心脏，皮肤和血液。4尽管嗅觉系统外的OR被认为参与了几个重要的生理和病理生理过程，包括寻路、细胞生长、迁移、分泌、分化和凋亡，4但对其在心血管系统中的功能的了解仍然很少。Ley及其同事在一项转录组学研究中意外地发现，在动脉粥样硬化主动脉的小鼠巨噬细胞中OR的高表达。他们扩展了这些发现，并证实OLFR 2在动脉粥样硬化主动脉和骨髓来源的巨噬细胞中表达，具有特定的生物学功能。辛醛是一种重要的OLFR 2配体，由脂质过氧化产生，并已在氧化低密度脂蛋白（oxLDL）中检测到，氧化低密度脂蛋白是动脉粥样硬化最重要的危险因素之一。这些结果表明辛醛和OLFR 2与动脉粥样硬化相关，鼓励作者研究OLFR 2的功能和调节，特别是其与动脉粥样硬化的相关性。
Hypercholesterolemia and high low-density lipoprotein (LDL) levels have been identified as a major risk factor of atherosclerotic cardiovascular disease (ASCVD), the leading cause of death in humans. LDL-lowering therapies effectively reduce ASCVD risk by~ 30-50% 2 and are recommended for primary and secondary prevention. However, a considerable number of patients with ASCVD show poor responses to LDL-lowering treatment; therefore, identifying and controlling additional risk factors are key to the reduction of ASCVD morbidity. Olfactory receptors (ORs) belong to a structurally diverse family of proteins capable of detecting a large spectrum of odorants in the environment. In vertebrates, including humans, ORs are typically located on the surface of sensory neurons in the olfactory epithelium. However, ORs also occur in tissues outside the olfactory epithelium. Parmentier et al. first identified OR gene transcripts expressed outside the olfactory epithelium in mammalian germ cells. 3 Subsequent studies have shown that ORs are also located in other human tissues, including the lungs, testis, intestines, heart, skin, and blood. 4 Although ORs outside the olfactory system are thought to participate in several essential physiological and pathophysiological processes, including pathfinding, cell growth, migration, secretion, differentiation, and apoptosis, 4 understanding of their functions in the cardiovascular system remains poor. Ley and colleagues unexpectedly found a high expression of ORs in mouse macrophages from the atherosclerotic aorta in a transcriptomic study. 5 They extended these findings and confirmed that OLFR2 was expressed in macrophages derived from atherosclerotic aorta and bone marrow, with specific biological functions. Octanal, an important OLFR2 ligand, is generated by lipid peroxidation and has been detected in oxidized low-density lipoprotein (oxLDL), which is one of the most important risk factors for atherosclerosis. These results suggest that octanal and OLFR2 are associated with atherosclerosis, encouraging the authors to investigate the function and regulation of OLFR2, and especially its relevance to atherosclerosis.
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影响因子：
20.1
作者：
McArdle, Sara;Buscher, Konrad;Ley, Klaus
通讯作者：
Ley, Klaus
影响因子：
56.9
作者：
Orecchioni, Marco;Kobiyama, Kouji;Winkels, Holger;Ghosheh, Yanal;McArdle, Sara;Mikulski, Zbigniew;Kiosses, William B.;Fan, Zhichao;Wen, Lai;Jung, Yunmin;Roy, Payel;Ali, Amal J.;Miyamoto, Yukiko;Mangan, Matthew;Makings, Jeffrey;Wang, Zhihao;Denn, Angela;Vallejo, Jenifer;Owens, Michaela;Durant, Christopher P.;Braumann, Simon;Mader, Navid;Li, Lin;Matsunami, Hiroaki;Eckmann, Lars;Latz, Eicke;Wang, Zeneng;Hazen, Stanley L.;Ley, Klaus
通讯作者：
Ley, Klaus
影响因子：
64.8
作者：
PARMENTIER, M;LIBERT, F;VASSART, G
通讯作者：
VASSART, G
影响因子：
168.9
作者：
Baigent, C.;Blackwell, L.;Emberson, J.;Holland, L. E.;Reith, C.;Bhala, N.;Peto, R.;Barnes, E. H.;Keech, A.;Simes, J.;Collins, R.
通讯作者：
Collins, R.