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Increased Intimal Hyperplasia After Vascular Injury in Male Androgen Receptor-Deficient Mice

Wilhelmson, Anna S K (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Wallenberglaboratoriet,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Wallenberg Laboratory
Fagman, Johan Bourghardt, 1980 (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Sahlgrenska Cancer Center,Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Wallenberg Laboratory,Institute of Clinical Sciences, Department of Surgery
Johansson, Inger, 1962 (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin,Wallenberg Laboratory,Institute of Medicine
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Zou, Zhiyuan V. (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin,Wallenberg Laboratory,Institute of Medicine
Andersson, Axel G (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin,Wallenberg Laboratory,Institute of Medicine
Svedlund Eriksson, Elin (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin,Wallenberglaboratoriet,Institute of Medicine,Wallenberg Laboratory
Johansson, Maria E, 1977 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
Lindahl, Per, 1967 (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
Fogelstrand, Per, 1971 (author)
Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine
Tivesten, Åsa, 1969 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Wallenberglaboratoriet,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Wallenberg Laboratory
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 (creator_code:org_t)
2016-08-17
2016
English.
In: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 157:10, s. 3915-3923
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

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