Pioglitazone attenuates valvular calcification induced by hypercholesterolemia
Open accessAbstract
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. Methods and 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. Conclusion—: 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.
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Pioglitazone, a PPARγ agonist, has been shown to reduce aortic valve calcification in mice, rabbit and swine models.
“Moreover, pioglitazone, a PPARγ agonist, has been shown to reduce aortic valve calcification in mice, rabbit and swine models.43,45,46”
From Transcriptomic signatures of calcific aortic valve stenosis severity in human tricuspid and bicuspid aortic valves (2025) · cites this paper as [46]
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- [41]Towler DA Shao JS Cheng SL Pingsterhaus JM Loewy AP Osteogenic regulation of vascular calcification. Ann NY Acad Sci 2006 1068 327 333 16831933
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- Authors
- Chu, Y., Lund, D. D., Weiss, R. M., Brooks, R. M., Doshi, H., Hajj, G. P., Sigmund, C. D., & Heistad, D. D.
- Affiliations
- University of Iowa (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2013-03
- Volume
- 33
- Issue
- 3
- Pages
- 523-532
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC3573264
- OpenAlex
- W2116298826
- Cited by
- 49
- References
- 61
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 7 · 2013: 3
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL062984, HL-62984)
- National Institute of Neurological Disorders and Stroke (NS24621, P01NS024621)
- National Center for Research Resources (RR 026293, S10RR026293)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- pioglitazone, calcific aortic stenosis, valve calcification, hypercholesterolemia, PPARγ, LDL receptor knockout mice, Western diet, lipid accumulation, apoptosis, caspase-3, valve function
- MeSH terms
- Pioglitazone, Serum Amyloid A Protein, Animals, Aorta, Aortic Valve, Aortic Valve Stenosis, Blood Glucose, Calcinosis, Cholesterol, Disease Models, Animal, Enzyme Activation, Female, Gene Expression Regulation, Hypercholesterolemia, Osteogenesis, Receptors, LDL, Time Factors, Ultrasonography, Biomarkers, Apoptosis, Mice, Knockout, In Situ Nick-End Labeling, Thiazolidinediones, PPAR gamma, Mice, Adiponectin, Caspase 3, Apolipoprotein B-100
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