{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:56:01Z","timestamp":1782284161128,"version":"3.54.5"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            Nifedipine, an L-type calcium channel blocker, protects against the progression of atherosclerosis. We investigated the molecular basis of the antiatherosclerotic effect of nifedipine in macrophages and apolipoprotein E-deficient mice.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            In macrophages, nifedipine increased peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3) activity without increasing PPAR\u03b3-binding activity. Amlodipine, another L-type calcium channel blocker, and 1,2-bis-(o-aminophenoxy)-ethane-N,N,-N\u2032,N\u2032-tetraacetic acid tetraacetoxy-methyl ester (BAPTA-AM), a calcium chelator, decreased PPAR\u03b3 activity, suggesting that nifedipine does not activate PPAR\u03b3 via calcium channel blocker activity. Inactivation of extracellular signal-regulated kinase 1\/2 suppressed PPAR\u03b32-Ser112 phosphorylation and induced PPAR\u03b3 activation. Nifedipine suppressed extracellular signal-regulated kinase 1\/2 activation and PPAR\u03b32-Ser112 phosphorylation, and mutating PPAR\u03b32-Ser112 to Ala abrogated nifedipine-mediated PPAR\u03b3 activation. These results suggested that nifedipine inhibited extracellular signal-regulated kinase 1\/2 activity and PPAR\u03b32-Ser112 phosphorylation, leading to PPAR\u03b3 activation. Nifedipine inhibited lipopolysaccharide-induced monocyte chemoattractant protein-1 expression and induced ATP-binding cassette transporter A1 mRNA expression, and these effects were abrogated by small interfering RNA for PPAR\u03b3. Furthermore, in apolipoprotein E-deficient mice, nifedipine treatment decreased atherosclerotic lesion size, phosphorylation of PPAR\u03b32-Ser112 and extracellular signal-regulated kinase 1\/2, and monocyte chemoattractant protein-1 mRNA expression and increased ATP-binding cassette transporter A1 expression in the aorta.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion\u2014<\/jats:italic>\n            <\/jats:bold>\n            Nifedipine unlike amlodipine inhibits PPAR\u03b3-Ser phosphorylation and activates PPAR\u03b3 to suppress monocyte chemoattractant protein-1 expression and induce ATP-binding cassette transporter A1 expression in macrophages. These effects may induce antiatherogenic effects in hypertensive patients.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.109.202309","type":"journal-article","created":{"date-parts":[[2010,5,28]],"date-time":"2010-05-28T02:40:36Z","timestamp":1275014436000},"page":"1598-1605","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Nifedipine Induces Peroxisome Proliferator-Activated Receptor-\u03b3 Activation in Macrophages and Suppresses the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice"],"prefix":"10.1161","volume":"30","author":[{"given":"Norio","family":"Ishii","sequence":"first","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan (T.K.); Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Matsumura","sequence":"additional","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan (T.K.); Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan (T.K.); Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Fukuda","sequence":"additional","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan (T.K.); Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Motoshima","sequence":"additional","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan (T.K.); Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Senokuchi","sequence":"additional","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan (T.K.); Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saya","family":"Nakao","sequence":"additional","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan (T.K.); Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuyuki","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan (T.K.); Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shokei","family":"Kim-Mitsuyama","sequence":"additional","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan (T.K.); Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruo","family":"Kawada","sequence":"additional","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan (T.K.); Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Takeya","sequence":"additional","affiliation":[{"name":"From the Departments of Metabolic Medicine (N.I., T.M., H.K., K.F., H.M., T.S., A.T., N.M., T.N., E.A.), Pharmacology and Molecular Therapeutics (S.K.-M.), and Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; 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