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Αλέξανδρος Γ. Σφακιανάκης

Monday, March 22, 2021

Laminar shear stress upregulates the expression of PPARs in vascular endothelial cells under high free fatty acid-induced stress

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Exp Ther Med. 2021 May;21(5):438. doi: 10.3892/etm.2021.9855. Epub 2021 Feb 26.

ABSTRACT

Shear stress has been reported to result in various metabolic effects in endothelial cells (ECs), which in turn contribute to the regulation of their vascular functions. Peroxisome proliferator-activated receptors (PPARs) have been reported to regulate lipid metabolism and have been implicated in metabolic disorders. The present study assessed the effects of laminar shear stress on the expression of PPARs in ECs in the presence of high concentrations of free fatty acids (FFAs). Human aortic ECs (HAECs) were treated with a high concentrations of palmitic acid (PA) and exposed to high shear stress (HSS) or low shear stress (LSS). Western blotting and ELISA were performed to quantify protein expression and assess prostacyclin production. The results revealed that long-term application of HSS to PA-treated HAECs induced PPAR-α, -δ and -γ protein exp ression. Additionally, LSS induced higher levels of PPAR-α protein expression in PA-treated HAECs compared with those after HSS. HAECs exposed to HSS also released prostacyclin (PGI2). However, HAECs treated with high concentrations of PA also produced high levels of PGI2 in the perfusion media in response to HSS compared with the static PA group. HSS also reduced the static PA-induced expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1. The results demonstrated that HAECs increases the expression of all three peroxisome proliferator-activated receptor isoforms in response to shear metabolic stress at high FFA concentrations. The present study may provide preliminary insights into the potential roles of PPARs as an effective treatment method against metabolic disturbances that can result in EC dysfunction.

PMID:33747175 | PMC:PMC7967849 | DOI:10.3892/etm.2021.9855

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