Rossignoli Aránzazu, Shang Ming-Mei, Gladh Hanna, Moessinger Christine, Foroughi Asl Hassan, Talukdar Husain Ahammad, Franzén Oscar, Mueller Steffen, Björkegren Johan L M, Folestad Erika, Skogsberg Josefin
From the Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (A.R., H.G., C.M., H.F.A., H.A.T., J.L.M.B., E.F., J.S.) and Unit of Computational Medicine, Department of Medicine (M.-M.S.), Karolinska Institutet, Stockholm, Sweden; Department of Genetics and Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY (O.F., J.L.M.B.); and Department of Molecular Genetics and Microbiology, Stony Brook University, New York, NY (S.M.).
Arterioscler Thromb Vasc Biol. 2017 Mar;37(3):534-542. doi: 10.1161/ATVBAHA.116.308715. Epub 2017 Jan 5.
Recently, poliovirus receptor-related 2 () emerged as a top gene in a global gene expression study aiming to detect plasma cholesterol-responsive genes causally related to atherosclerosis regression in hypercholesterolemic mice. PVRL2 is an adherens junction protein implied to play a role in transendothelial migration of leukocytes, a key feature in atherosclerosis development. In this study, we investigated the effect of deficiency on atherosclerosis development and transendothelial migration of leukocytes activity. APPROACH AND RESULTS: -deficient mice bred onto an atherosclerosis-prone background () had less atherosclerotic lesions and more stable plaques compared with littermate controls (). mice also showed a 49% decrease in transendothelial migration of leukocytes activity observed using the in vivo air pouch model. In accordance, augmented arterial wall expression of during atherosclerosis progression coincided with an increased gene expression of migrating leukocytes into the vessel wall. Both in human and mice, gene and protein expression of PVRL2 was predominantly observed in the vascular endothelium according to the immunohistochemical and gene expression data. In addition, the cholesterol responsiveness of was also observed in humans.
PVRL2 is a plasma cholesterol-responsive gene acting at endothelial sites of vascular inflammation that could potentially be a new therapeutic target for atherosclerosis prevention through its suggested transendothelial migration of leukocytes modulating activity.
最近，脊髓灰质炎病毒受体相关蛋白2（PVRL2）在一项全球基因表达研究中成为关键基因，该研究旨在检测与高胆固醇血症小鼠动脉粥样硬化消退有因果关系的血浆胆固醇反应性基因。PVRL2是一种黏附连接蛋白，被认为在白细胞跨内皮迁移中起作用，而白细胞跨内皮迁移是动脉粥样硬化发展的一个关键特征。在本研究中，我们调查了PVRL2缺乏对动脉粥样硬化发展和白细胞跨内皮迁移活性的影响。
与同窝对照小鼠相比，在易患动脉粥样硬化背景（ApoE−/−）下培育的PVRL2基因敲除小鼠的动脉粥样硬化病变较少，斑块更稳定。使用体内气袋模型观察到，PVRL2基因敲除小鼠的白细胞跨内皮迁移活性也降低了49%。相应地，在动脉粥样硬化进展过程中，动脉壁PVRL2表达增加与迁移到血管壁的白细胞基因表达增加相一致。根据免疫组织化学和基因表达数据，在人和小鼠中，PVRL2的基因和蛋白表达主要在血管内皮中观察到。此外，在人类中也观察到PVRL2的胆固醇反应性。
PVRL2是一种在血管炎症内皮部位起作用的血浆胆固醇反应性基因，通过其调节白细胞跨内皮迁移的活性，可能成为预防动脉粥样硬化的新治疗靶点。
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