{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:06:37Z","timestamp":1791176797621,"version":"4.1.0"},"reference-count":43,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mineralocorticoid receptor (MR) activation is proinflammatory and proatherogenic. Antagonism of MR improves survival in humans with congestive heart failure caused by atherosclerotic disease. In animal models, activation of MR exacerbates atherosclerosis. The enzyme 11\u03b2-hydroxysteroid dehydrogenase type 2 (11\u03b2-HSD2) prevents inappropriate activation of the MR by inactivating glucocorticoids in mineralocorticoid-target tissues. To determine whether glucocorticoid-mediated activation of MR increases atheromatous plaque formation, we generated Apoe\u2212\/\u2212\/11\u03b2-HSD2\u2212\/\u2212 double-knockout (E\/b2) mice. On chow diet, E\/b2 mice developed atherosclerotic lesions by 3 months of age, whereas Apolipoprotein E (Apoe\u2212\/\u2212) mice remained lesion free. Brachiocephalic plaques in 3-month-old E\/b2 mice showed increased macrophage and lipid content and reduced collagen content compared with similar sized brachiocephalic plaques in 6-month-old Apoe\u2212\/\u2212 mice. Crucially, treatment of E\/b2 mice with eplerenone, an MR antagonist, reduced plaque development and macrophage infiltration while increasing collagen and smooth muscle cell content without any effect on systolic blood pressure. In contrast, reduction of systolic blood pressure in E\/b2 mice using the epithelial sodium channel blocker amiloride produced a less-profound atheroprotective effect. Vascular cell adhesion molecule 1 expression was increased in the endothelium of E\/b2 mice compared with Apoe\u2212\/\u2212 mice. Similarly, aldosterone increased vascular cell adhesion molecule 1 expression in mouse aortic endothelial cells, an effect mimicked by corticosterone only in the presence of an 11\u03b2-HSD2 inhibitor. Thus, loss of 11\u03b2-HSD2 leads to striking atherogenesis associated with activation of MR, stimulating proinflammatory processes in the endothelium of E\/b2 mice.<\/jats:p>","DOI":"10.1210\/en.2010-0925","type":"journal-article","created":{"date-parts":[[2010,11,25]],"date-time":"2010-11-25T03:40:21Z","timestamp":1290656421000},"page":"236-246","source":"Crossref","is-referenced-by-count":88,"title":["11\u03b2-Hydroxysteroid Dehydrogenase Type 2 Deficiency Accelerates Atherogenesis and Causes Proinflammatory Changes in the Endothelium in Apoe\u2212\/\u2212 Mice"],"prefix":"10.1210","volume":"152","author":[{"given":"Graeme A.","family":"Deuchar","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (G.A.D., D.M., P.W.F.H., D.G.B., D.J.W., J.J.M., K.C., J.R.S.), The Queen\u2019s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"McLean","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (G.A.D., D.M., P.W.F.H., D.G.B., D.J.W., J.J.M., K.C., J.R.S.), The Queen\u2019s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick W. F.","family":"Hadoke","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (G.A.D., D.M., P.W.F.H., D.G.B., D.J.W., J.J.M., K.C., J.R.S.), The Queen\u2019s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Brownstein","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (G.A.D., D.M., P.W.F.H., D.G.B., D.J.W., J.J.M., K.C., J.R.S.), The Queen\u2019s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Webb","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (G.A.D., D.M., P.W.F.H., D.G.B., D.J.W., J.J.M., K.C., J.R.S.), The Queen\u2019s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Mullins","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (G.A.D., D.M., P.W.F.H., D.G.B., D.J.W., J.J.M., K.C., J.R.S.), The Queen\u2019s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Chapman","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (G.A.D., D.M., P.W.F.H., D.G.B., D.J.W., J.J.M., K.C., J.R.S.), The Queen\u2019s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Seckl","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (G.A.D., D.M., P.W.F.H., D.G.B., D.J.W., J.J.M., K.C., J.R.S.), The Queen\u2019s Medical Research Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri V.","family":"Kotelevtsev","sequence":"first","affiliation":[{"name":"Puschino State University (Y.V.K.), 142292 Russia, Puschino, Moscow Region"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612484630700_R1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1056\/NEJM199909023411001","article-title":"The effect of spironolactone on morbidity and mortality in patients with severe heart failure. 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