{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:29:49Z","timestamp":1792704589271,"version":"4.5.0"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2013,1,23]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Aldosterone levels correlate with the incidence of myocardial infarction and mortality in cardiovascular patients. Aldosterone promotes atherosclerosis in animal models, but the mechanisms are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Aldosterone was infused to achieve pathologically relevant levels that did not increase blood pressure in the atherosclerosis\u2010prone apolipoprotein E\u2013knockout mouse (ApoE\u2212\/\u2212). Aldosterone increased atherosclerosis in the aortic root 1.8\u00b10.1\u2010fold after 4\u00a0weeks and in the aortic arch 3.7\u00b10.2\u2010fold after 8\u00a0weeks, without significantly affecting plaque size in the abdominal aorta or traditional cardiac risk factors. Aldosterone treatment increased lipid content of plaques (2.1\u00b10.2\u2010fold) and inflammatory cell content (2.2\u00b10.3\u2010fold), induced early T\u2010cell (2.9\u00b10.3\u2010fold) and monocyte (2.3\u00b10.3\u2010fold) infiltration into atherosclerosis\u2010prone vascular regions, and enhanced systemic inflammation with increased spleen weight (1.52\u00b10.06\u2010fold) and the circulating cytokine\n                      <jats:styled-content style=\"fixed-case\">RANTES<\/jats:styled-content>\n                      (regulated and normal T cell secreted; 1.6\u00b10.1\u2010fold). To explore the mechanism, 7 genes were examined for aldosterone regulation in the ApoE\u2212\/\u2212 aorta. Further studies focused on the proinflammatory placental growth factor (Pl\n                      <jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content>\n                      ), which was released from aldosterone\u2010treated ApoE\u2212\/\u2212 vessels. Activation of the mineralocorticoid receptor by aldosterone in human coronary artery smooth muscle cells (\n                      <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>\n                      s) caused the release of factors that promote monocyte chemotaxis, which was inhibited by blocking monocyte Pl\n                      <jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content>\n                      receptors. Furthermore, Pl\n                      <jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content>\n                      \u2010deficient ApoE\u2212\/\u2212 mice were resistant to early aldosterone\u2010induced increases in plaque burden and inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Aldosterone increases early atherosclerosis in regions of turbulent blood flow and promotes an inflammatory plaque phenotype that is associated with rupture in humans. The mechanism may involve\n                      <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>\n                      release of soluble factors that recruit activated leukocytes to the vessel wall via Pl\n                      <jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content>\n                      signaling. These findings identify a novel mechanism and potential treatment target for aldosterone\u2010induced ischemia in humans.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.112.000018","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T12:49:11Z","timestamp":1369399751000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":110,"title":["Aldosterone Increases Early Atherosclerosis and Promotes Plaque Inflammation Through a Placental Growth Factor\u2010Dependent Mechanism"],"prefix":"10.1161","volume":"2","author":[{"given":"Adam P.","family":"McGraw","sequence":"first","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessamyn","family":"Bagley","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA"},{"name":"Translational Immunology Science Center, Tufts Medical Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Galayda","sequence":"additional","affiliation":[{"name":"Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Nickerson","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Armani","sequence":"additional","affiliation":[{"name":"Centre for Clinical and Basic Research, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Caprio","sequence":"additional","affiliation":[{"name":"Centre for Clinical and Basic Research, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Carmeliet","sequence":"additional","affiliation":[{"name":"Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center (VRC), Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium"},{"name":"Laboratory of Angiogenesis and Neurovascular Link, VRC, Katholieke Universiteit Leuven (K.U. 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