title: Increased Intimal Hyperplasia After Vascular Injury in Male Androgen Receptor-Deficient Mice.
abstract: Intimal hyperplasia is a vascular pathological process involved in the pathogenesis of atherosclerosis. Data suggest that T, the most important sex steroid hormone in males, protects men from atherosclerotic cardiovascular disease. T mainly acts via the androgen receptor (AR), and in this study we evaluated formation of intimal hyperplasia in male AR knockout (ARKO) mice using a vascular injury model. Two weeks after ligation of the carotid artery, male ARKO mice showed increased intimal area and intimal thickness compared with controls. After endothelial denudation by an in vivo scraping injury, there was no difference in the reendothelialization in ARKO compared with control mice. Ex vivo, we observed increased outgrowth of vascular smooth muscle cells from ARKO compared with control aortic tissue explants; the number of outgrown cells was almost doubled in ARKO. In vitro, stimulation of human aortic vascular smooth muscle cells with a physiological T concentration inhibited both migration and proliferation of the cells. Analyzing the expression of central regulators of cell proliferation and migration, we found that mRNA and protein levels of p27 were lower in uninjured arteries from ARKO mice and that T replacement to castrated male mice increased p27 mRNA in an AR-dependent manner. In conclusion, AR deficiency in male mice increases intimal hyperplasia in response to vascular injury, potentially related to the effects of androgens/AR to inhibit proliferation and migration of smooth muscle cells.
authors.affiliation: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., J.B.F., I.J., Z.V.Z., A.G.A., E.S.E., P.L., P.F., Å.T.), Institute of Medicine; Sahlgrenska Cancer Center (J.B.F.), Department of Surgery, Institute of Clinical Sciences; and Department of Physiology (M.E.J.), Institute of Neuroscience and Physiology; Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; The Finsen Laboratory (A.S.W), Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Centre, Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Wilhelmson
authors.affiliation: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., J.B.F., I.J., Z.V.Z., A.G.A., E.S.E., P.L., P.F., Å.T.), Institute of Medicine; Sahlgrenska Cancer Center (J.B.F.), Department of Surgery, Institute of Clinical Sciences; and Department of Physiology (M.E.J.), Institute of Neuroscience and Physiology; Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; The Finsen Laboratory (A.S.W), Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Centre, Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Johan B
authors.initials: JB
authors.lastname: Fagman
authors.affiliation: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., J.B.F., I.J., Z.V.Z., A.G.A., E.S.E., P.L., P.F., Å.T.), Institute of Medicine; Sahlgrenska Cancer Center (J.B.F.), Department of Surgery, Institute of Clinical Sciences; and Department of Physiology (M.E.J.), Institute of Neuroscience and Physiology; Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; The Finsen Laboratory (A.S.W), Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Centre, Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Inger
authors.initials: I
authors.lastname: Johansson
authors.affiliation: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., J.B.F., I.J., Z.V.Z., A.G.A., E.S.E., P.L., P.F., Å.T.), Institute of Medicine; Sahlgrenska Cancer Center (J.B.F.), Department of Surgery, Institute of Clinical Sciences; and Department of Physiology (M.E.J.), Institute of Neuroscience and Physiology; Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; The Finsen Laboratory (A.S.W), Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Centre, Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Zhiyuan V
authors.initials: ZV
authors.lastname: Zou
authors.affiliation: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., J.B.F., I.J., Z.V.Z., A.G.A., E.S.E., P.L., P.F., Å.T.), Institute of Medicine; Sahlgrenska Cancer Center (J.B.F.), Department of Surgery, Institute of Clinical Sciences; and Department of Physiology (M.E.J.), Institute of Neuroscience and Physiology; Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; The Finsen Laboratory (A.S.W), Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Centre, Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Axel G
authors.initials: AG
authors.lastname: Andersson
authors.affiliation: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., J.B.F., I.J., Z.V.Z., A.G.A., E.S.E., P.L., P.F., Å.T.), Institute of Medicine; Sahlgrenska Cancer Center (J.B.F.), Department of Surgery, Institute of Clinical Sciences; and Department of Physiology (M.E.J.), Institute of Neuroscience and Physiology; Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; The Finsen Laboratory (A.S.W), Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Centre, Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Elin
authors.initials: E
authors.lastname: Svedlund Eriksson
authors.affiliation: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., J.B.F., I.J., Z.V.Z., A.G.A., E.S.E., P.L., P.F., Å.T.), Institute of Medicine; Sahlgrenska Cancer Center (J.B.F.), Department of Surgery, Institute of Clinical Sciences; and Department of Physiology (M.E.J.), Institute of Neuroscience and Physiology; Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; The Finsen Laboratory (A.S.W), Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Centre, Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., J.B.F., I.J., Z.V.Z., A.G.A., E.S.E., P.L., P.F., Å.T.), Institute of Medicine; Sahlgrenska Cancer Center (J.B.F.), Department of Surgery, Institute of Clinical Sciences; and Department of Physiology (M.E.J.), Institute of Neuroscience and Physiology; Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; The Finsen Laboratory (A.S.W), Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Centre, Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Lindahl
authors.affiliation: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., J.B.F., I.J., Z.V.Z., A.G.A., E.S.E., P.L., P.F., Å.T.), Institute of Medicine; Sahlgrenska Cancer Center (J.B.F.), Department of Surgery, Institute of Clinical Sciences; and Department of Physiology (M.E.J.), Institute of Neuroscience and Physiology; Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; The Finsen Laboratory (A.S.W), Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Centre, Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Fogelstrand
authors.affiliation: Wallenberg Laboratory for Cardiovascular and Metabolic Research (A.S.W., J.B.F., I.J., Z.V.Z., A.G.A., E.S.E., P.L., P.F., Å.T.), Institute of Medicine; Sahlgrenska Cancer Center (J.B.F.), Department of Surgery, Institute of Clinical Sciences; and Department of Physiology (M.E.J.), Institute of Neuroscience and Physiology; Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden; The Finsen Laboratory (A.S.W), Rigshospitalet, Faculty of Health Sciences, Biotech Research and Innovation Centre, Danish Stem Cell Centre (DanStem), Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Tivesten
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000150:complications* / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D058426:Neointima / Q000209:etiology* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
chemical_list: D011944:Receptors, Androgen; D050760:Cyclin-Dependent Kinase Inhibitor p27; D013739:Testosterone