title: Pioglitazone attenuates valvular calcification induced by hypercholesterolemia.
abstract: OBJECTIVE
  Development of calcific aortic valve stenosis involves multiple signaling pathways, which may be modulated by peroxisome proliferator-activated receptor-γ). This study tested the hypothesis that pioglitazone (Pio), a ligand for peroxisome proliferator-activated receptor-γ, inhibits calcification of the aortic valve in hypercholesteremic mice.
  
  
  RESULTS
  Low density lipoprotein receptor(-/-)/apolipoprotein B(100/100) 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.
  
  
  CONCLUSIONS
  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-γ ligands may be useful for early intervention to prevent or slow stenosis of aortic valves.
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chu
authors.forename: Donald D
authors.initials: DD
authors.lastname: Lund
authors.forename: Robert M
authors.initials: RM
authors.lastname: Weiss
authors.forename: Robert M
authors.initials: RM
authors.lastname: Brooks
authors.forename: Hardik
authors.initials: H
authors.lastname: Doshi
authors.forename: Georges P
authors.initials: GP
authors.lastname: Hajj
authors.forename: Curt D
authors.initials: CD
authors.lastname: Sigmund
authors.forename: Donald D
authors.initials: DD
authors.lastname: Heistad
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D053299:Apolipoprotein B-100 / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002114:Calcinosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation; D006937:Hypercholesterolemia / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D000077205:Pioglitazone; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D000685:Serum Amyloid A Protein / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D053299:Apolipoprotein B-100; D015415:Biomarkers; D001786:Blood Glucose; D047495:PPAR gamma; D011973:Receptors, LDL; D000685:Serum Amyloid A Protein; D045162:Thiazolidinediones; D002784:Cholesterol; C505409:Casp3 protein, mouse; D053148:Caspase 3; D000077205:Pioglitazone