title: Lim domain binding 2: a key driver of transendothelial migration of leukocytes and atherosclerosis.
abstract: OBJECTIVE
  Using a multi-tissue, genome-wide gene expression approach, we recently identified a gene module linked to the extent of human atherosclerosis. This atherosclerosis module was enriched with inherited risk for coronary and carotid artery disease (CAD) and overlapped with genes in the transendothelial migration of leukocyte (TEML) pathway. Among the atherosclerosis module genes, the transcription cofactor Lim domain binding 2 (LDB2) was the most connected in a CAD vascular wall regulatory gene network. Here, we used human genomics and atherosclerosis-prone mice to evaluate the possible role of LDB2 in TEML and atherosclerosis.
  
  
  RESULTS
  mRNA profiles generated from blood macrophages in patients with CAD were used to infer transcription factor regulatory gene networks; Ldlr(-/-)Apob(100/100) mice were used to study the effects of Ldb2 deficiency on TEML activity and atherogenesis. LDB2 was the most connected gene in a transcription factor regulatory network inferred from TEML and atherosclerosis module genes in CAD macrophages. In Ldlr(-/-)Apob(100/100) mice, loss of Ldb2 increased atherosclerotic lesion size ≈2-fold and decreased plaque stability. The exacerbated atherosclerosis was caused by increased TEML activity, as demonstrated in air-pouch and retinal vasculature models in vivo, by ex vivo perfusion of primary leukocytes, and by leukocyte migration in vitro. In THP1 cells, migration was increased by overexpression and decreased by small interfering RNA inhibition of LDB2. A functional LDB2 variant (rs10939673) was associated with the risk and extent of CAD across several cohorts.
  
  
  CONCLUSIONS
  As a key driver of the TEML pathway in CAD macrophages, LDB2 is a novel candidate to target CAD by inhibiting the overall activity of TEML.
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Ming-Mei
authors.initials: MM
authors.lastname: Shang
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Husain A
authors.initials: HA
authors.lastname: Talukdar
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hofmann
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Colin
authors.initials: C
authors.lastname: Niaudet
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Hassan Foroughi
authors.initials: HF
authors.lastname: Asl
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Jain
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Rossignoli
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cedergren
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Angela
authors.initials: A
authors.lastname: Silveira
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Bruna
authors.initials: B
authors.lastname: Gigante
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Karin
authors.initials: K
authors.lastname: Leander
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Arno
authors.initials: A
authors.lastname: Ruusalepp
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Ivert
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Tom
authors.initials: T
authors.lastname: Michoel
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Eric E
authors.initials: EE
authors.lastname: Schadt
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.).
authors.forename: Josefin
authors.initials: J
authors.lastname: Skogsberg
authors.affiliation: From the Division of Cardiovascular Genomics (M.M.S., H.A.T., H.F.A., A.R., C.C., J.S., J.L.M.B.), Division of Vascular Biology, Department of Medical Biochemistry and Biophysics (M.M.S., H.A.T., J.J.H., C.N., H.F.A., A.R., C.C., C.B., J.S., J.L.M.B.), Computational Medicine Unit, Department of Medicine Solna, Center of Molecular Medicine (M.M.S.), and Department of Environmental Medicine (B.G., K.L., U.d.F.), Karolinska Institutet, Solna, Sweden; Clinical Gene Networks AB, Karolinska Science Park, Solna, Sweden (M.M.S., A.R., J.L.M.B.); Division of Cardiovascular Genomics, Department of Pathological Anatomy and Forensic Medicine, University of Tartu, Tartu, Estonia (R.K.J., A.R., J.L.M.B.); Cardiovascular Genetics and Genomics, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden (A.S., A.H.); Department of Cardiac Surgery, Tartu University Hospital, Tartu, Estonia (A.R.); Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Clinical Research Center, Skåne University Hospital, Malmö, Sweden (O.M.); Department of Cardiothoracic Surgery and Anesthesiology and Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Sweden (T.I.); School of Life Sciences-LifeNet, Freiburg Institute for Advanced Studies, University of Freiburg, Freiburg im Breisgau, Germany (T.M.); The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, United Kingdom (T.M.); and Institute for Genomics and Multi-Scale Biology, Mount Sinai School of Medicine, New York, NY (E.E.S., J.L.M.B.). johan.bjorkegren@ki.se.
authors.forename: Johan L M
authors.initials: JL
authors.lastname: Björkegren
mesh_terms: D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics; D050197:Atherosclerosis / Q000503:physiopathology*; D002340:Carotid Artery Diseases / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003324:Coronary Artery Disease / Q000235:genetics / Q000473:pathology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D060588:LIM Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics / Q000502:physiology*
chemical_list: D053299:Apolipoprotein B-100; D018932:Chemokine CCL2; C484572:LDB2 protein, human; D060588:LIM Domain Proteins; C106649:Ldb2 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors
keywords: atherosclerosis; coronary artery disease; gene regulatory networks