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Aleksandra Piechota-Polanczyk

Jagiellonian University, Poland

Title: Involvement of Nrf2 transcriptional activity in the induction of HO1 in abdominal aortic aneurysm wall of simvastatin treated patients


Biography: Aleksandra Piechota-Polanczyk


Statement of the Problem: Lack of Nrf2-regulated antioxidative heme oxygenase-1 (HO-1) may exacerbate abdominal aortic aneurysm (AAA). However, the effect of simvastatin on Nrf2/HO-1 pathway in patients with AAA has not been studied yet.
Methodology & Theoretical Orientation: We analyzed the localization of Nrf2 and HO-1 in human AAA wall and verified the influence of simvastatin treatment on Nrf2. We took AAA tissue from patients treated with simvastatin (N=28) or without statins (N=14) and verified the effect of simvastatin on primary human aortic endothelial (EC) and smooth muscle cells (SMC).
Findings: We found a positive correlation between expression of gene and glutathione (GSH) in AAA wall. Both, HMOX-1 and GSH are regulated by Nrf2. However, the expression of Nrf2 and HO-1 seemed not to colocalize in AAA wall. Simvastatin treatment up-regulated HO-1 in AAA, but Nrf2 level was only higher in vasa vasorum. In vitro studies showed that simvastatin raises HO-1 protein in EC and SMC but independently on NFE2L2.
Conclusion & Significance: Simvastatin-induced modulation of HO-1 in ECs and SMCs in vitro is not related to Nrf2/ARE activity. Different HO-1 and Nrf2 localization together with stable expression of Nrf2 target genes in AAA tissue signify Nrf2- independency.