Clinical & Experimental Cardiology
Open Access

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

Joint Event on 3^rd International Conference on Cardiovascular Medicine and Cardiac Surgery & 26^th Annual Conference on Clinical & Medical Case Reports in Cardiology

July 05-06, 2018 | Berlin, Germany

Aleksandra Piechota-Polanczyk, Aleksandra Kopacz, Damian Kloska, Anna Grochot-Przeczek, Ihor Huk and Alicja Jozkowicz

Jagiellonian University, Poland
University of Agriculture in Krakow, Poland
Medical University of Vienna, Austria

Scientific Tracks Abstracts: J Clin Exp Cardiolog

Abstract :

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.
Recent Publications
1. Loboda (2017) Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cellular and Molecular Life Sciences 73(17): 3221-47.
2. Rodella (2016) Abdominal aortic aneurysm and histological, clinical, radiological correlation. Acta Histochemica 118(3):256-62.
3. Piechota-Polanczyk and Jozkowicz (2016) The role of statins in heme oxygenase-1 activation in cardiovascular diseases. Current Drug Targets 18(6): 674-686.
4. Pantan (2016) Synergistic effect of atorvastatin and Cyanidin-3-glucoside on angiotensin II-induced inflammation in vascular smooth muscle cells. Experimental Cell Research 342(25):104-112.
5. Jez M (2017) Valproic acid downregulates heme oxygenase-1 independently of Nrf2 by increasing ubiquitination and proteasomal degradation. Biochemical and Biophysical Research Communications 485(8):160-166.