The PPAR-γ Agonist Pioglitazone Modulates Proliferation and Migration in HUVEC, HAOSMC and Human Arteriovenous Fistula-Derived Cells.
Carmen CiavarellaIlenia MottaFrancesco VasuriTeresa PalumboAnthony Paul LisiAlice CostaAnnalisa AstolfiSabrina ValentePiera VersuraEugenio F FornasieroRaffaella MauroMauro GargiuloGianandrea PasquinelliPublished in: International journal of molecular sciences (2023)
The failure of arteriovenous fistulas (AVFs) following intimal hyperplasia (IH) increases morbidity and mortality rates in patients undergoing hemodialysis for chronic kidney disease. The peroxisome-proliferator associated receptor (PPAR-γ) may be a therapeutic target in IH regulation. In the present study, we investigated PPAR-γ expression and tested the effect of pioglitazone, a PPAR-γ agonist, in different cell types involved in IH. As cell models, we used Human Endothelial Umbilical Vein Cells (HUVEC), Human Aortic Smooth Muscle Cells (HAOSMC), and AVF cells (AVFCs) isolated from (i) normal veins collected at the first AVF establishment (T0), and (ii) failed AVF with IH (T1). PPAR-γ was downregulated in AVF T1 tissues and cells, in comparison to T0 group. HUVEC, HAOSMC, and AVFC (T0 and T1) proliferation and migration were analyzed after pioglitazone administration, alone or in combination with the PPAR-γ inhibitor, GW9662. Pioglitazone negatively regulated HUVEC and HAOSMC proliferation and migration. The effect was antagonized by GW9662. These data were confirmed in AVFCs T1, where pioglitazone induced PPAR-γ expression and downregulated the invasive genes SLUG, MMP-9, and VIMENTIN. In summary, PPAR-γ modulation may represent a promising strategy to reduce the AVF failure risk by modulating cell proliferation and migration.
Keyphrases
- induced apoptosis
- endothelial cells
- insulin resistance
- cell cycle arrest
- chronic kidney disease
- patients undergoing
- fatty acid
- signaling pathway
- cell therapy
- single cell
- end stage renal disease
- machine learning
- cell death
- adipose tissue
- electronic health record
- cell proliferation
- skeletal muscle
- aortic valve
- pi k akt
- long non coding rna
- pluripotent stem cells
- left ventricular
- atrial fibrillation
- drug induced
- pulmonary artery
- atomic force microscopy
- cell migration
- data analysis
- stress induced