{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:27:10Z","timestamp":1792445230476,"version":"4.5.0"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Development of calcific aortic valve stenosis involves multiple signaling pathways, which may be modulated by peroxisome proliferator-activated receptor-\u03b3). This study tested the hypothesis that pioglitazone (Pio), a ligand for peroxisome proliferator-activated receptor-\u03b3, inhibits calcification of the aortic valve in hypercholesteremic mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Low density lipoprotein receptor\n              <jats:sup>\u2013\/\u2013<\/jats:sup>\n              \/apolipoprotein B\n              <jats:sup>100\/100<\/jats:sup>\n              mice were fed a Western-type diet with or without Pio (20 mg\/kg per day) for 6 months. Pio attenuated lipid deposition and calcification in the aortic valve, but not aorta. In the aortic valve, Pio reduced levels of active caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Valve function (echocardiography) was significantly improved by Pio. To determine whether changes in gene expression are associated with differential effects of Pio on aortic valves versus aorta, Reversa mice were fed Western diet with or without Pio for 2 months. Several procalcific genes were increased by Western diet, and the increase was attenuated by Pio, in aortic valve, but not aorta.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>Pio attenuates lipid deposition, calcification, and apoptosis in aortic valves of hypercholesterolemic mice, improves aortic valve function, and exhibits preferential effects on aortic valves versus aorta. We suggest that Pio protects against calcific aortic valve stenosis, and Pio or other peroxisome proliferator-activated receptor-\u03b3 ligands may be useful for early intervention to prevent or slow stenosis of aortic valves.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.112.300794","type":"journal-article","created":{"date-parts":[[2013,1,4]],"date-time":"2013-01-04T06:57:33Z","timestamp":1357282653000},"page":"523-532","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Pioglitazone Attenuates Valvular Calcification Induced by Hypercholesterolemia"],"prefix":"10.1161","volume":"33","author":[{"given":"Yi","family":"Chu","sequence":"first","affiliation":[{"name":"From the Departments of Internal Medicine (Y.C., D.D.L., R.M.W., R.M.B., H.D., G.P.H., C.D.S., D.D.H.) and Pharmacology (C.D.S., D.D.H.), University of Iowa Carver College of Medicine, Iowa City, IA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald D.","family":"Lund","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (Y.C., D.D.L., R.M.W., R.M.B., H.D., G.P.H., C.D.S., D.D.H.) and Pharmacology (C.D.S., D.D.H.), University of Iowa Carver College of Medicine, Iowa City, IA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Weiss","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (Y.C., D.D.L., R.M.W., R.M.B., H.D., G.P.H., C.D.S., D.D.H.) and Pharmacology (C.D.S., D.D.H.), University of Iowa Carver College of Medicine, Iowa City, IA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Brooks","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (Y.C., D.D.L., R.M.W., R.M.B., H.D., G.P.H., C.D.S., D.D.H.) and Pharmacology (C.D.S., D.D.H.), University of Iowa Carver College of Medicine, Iowa City, IA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardik","family":"Doshi","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (Y.C., D.D.L., R.M.W., R.M.B., H.D., G.P.H., C.D.S., D.D.H.) and Pharmacology (C.D.S., D.D.H.), University of Iowa Carver College of Medicine, Iowa City, IA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges P.","family":"Hajj","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (Y.C., D.D.L., R.M.W., R.M.B., H.D., G.P.H., C.D.S., D.D.H.) and Pharmacology (C.D.S., D.D.H.), University of Iowa Carver College of Medicine, Iowa City, IA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curt D.","family":"Sigmund","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (Y.C., D.D.L., R.M.W., R.M.B., H.D., G.P.H., C.D.S., D.D.H.) and Pharmacology (C.D.S., D.D.H.), University of Iowa Carver College of Medicine, Iowa City, IA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald D.","family":"Heistad","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (Y.C., D.D.L., R.M.W., R.M.B., H.D., G.P.H., C.D.S., D.D.H.) and Pharmacology (C.D.S., D.D.H.), University of Iowa Carver College of Medicine, Iowa City, IA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.90.2.844"},{"key":"e_1_3_4_3_2","first-page":"254","article-title":"Identification and characterization of calcifying valve cells from human and canine aortic valves.","volume":"8","author":"Mohler ER","year":"1999","unstructured":"Mohler ER, Chawla MK, Chang AW, Vyavahare N, Levy RJ, Graham L, Gannon FH. 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