Poliovirus Receptor-Related 2: A Cholesterol-Responsive Gene Affecting Atherosclerosis Development by Modulating Leukocyte Migration.

Autor:	Rossignoli A; 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.). Erika.folestad@ki.se Aranzazu.rossignoli@ki.se., Shang MM; 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.)., Gladh H; 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.)., Moessinger C; 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.)., Foroughi Asl H; 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.)., Talukdar HA; 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.)., Franzén O; 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.)., Mueller S; 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.)., Björkegren JL; 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.)., Folestad E; 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.)., Skogsberg J; 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.). Erika.folestad@ki.se Aranzazu.rossignoli@ki.se.
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2017 Mar; Vol. 37 (3), pp. 534-542. Date of Electronic Publication: 2017 Jan 05.
DOI:	10.1161/ATVBAHA.116.308715
Abstrakt:	Objective: Recently, poliovirus receptor-related 2 ( Pvrl2 ) 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 Pvrl2 deficiency on atherosclerosis development and transendothelial migration of leukocytes activity. APPROACH AND RESULTS: Pvrl2 -deficient mice bred onto an atherosclerosis-prone background ( Pvrl2 -/- Ldlr -/- Apob 100/100 ) had less atherosclerotic lesions and more stable plaques compared with littermate controls ( Pvrl2 +/+ Ldlr -/- Apob 100/100 ). Pvrl2 -/- Ldlr -/- Apob 100/100 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 Pvrl2 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 PVRL2 was also observed in humans. Conclusions: 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. (© 2017 American Heart Association, Inc.)
Databáze:	MEDLINE
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