The Influence of Simvastatin on NGAL, Matrix Metalloproteinases and Their Tissue Inhibitors in Human Intraluminal Thrombus and Abdominal Aortic Aneurysm Tissue

Piechota-Polańczyk, Aleksandra; Demyanets, Svitlana; Mittlböck, Martina; Hofmann, Melanie; Domenig, Christoph; Neumayer, Christoph; Wojta, Johann; Klinger, Markus; Nanobachvili, Josif; Huk, Ihor

doi:10.1016/j.ejvs.2015.02.011

Cited by 23 publications

(16 citation statements)

References 35 publications

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“…MAPK signaling pathway is a cellular pathway consisting of a large number of proteins that can be activated by a variety of extracellular stimuli. Activation of the MAPK pathway can result in a multitude of physiological effects, including apoptosis, cell proliferation, mitosis and the transcription of several classes of genes [20].…”

Section: Discussionmentioning

confidence: 99%

Microarray expression profile analysis of long non‐coding RNAs in thoracic aortic aneurysm

Yang¹,

Yang

2017

The Kaohsiung J of Med Scie

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Thoracic aortic aneurysm (TAA) is a highly lethal vascular disease. Long non-coding RNAs (lncRNAs) are newly discovered as a regulator of protein genes and play critical roles in cardiovascular physio-pathological processes. However, there were a few studies looking at lncRNAs in TAA. In this study, we profiled differential expression of lncRNAs between TAA (TAA group, N = 6) and normal thoracic aorta (control group, n = 6) by third-generation lncRNA microarray. We identified 1352 up-regulated and 1624 down-regulated lncRNAs with differential expression (log fold-change > 2.0, p < 0.01). Through nearby protein-coding gene associated with extracellular matrix (ECM) metabolism and vascular smooth muscle cell (VSMC) apoptosis, 12 up-regulated and 9 down-regulated lncRNAs were selected for further analysis. By calculating phastCons score of base, we identified 8 candidate lncRNAs (4 up-regulated and 4 down-regulated) with high conservation across species. By tissue specificity analysis, we found that 5 lncRNAs (HIF1A-AS1, RP11-465L10.10, LOC100506472, CTD-2184D3.5 and RP-399O19.5) were highly expressed in aortic tissues, suggested that they may be closely associated with TAA. Among them, 2 lncRNAs (RP11-465L10.10 and CTD-2184D3.5) with higher specificity in aorta (p < 0.01) were analyzed by bioinformatics. Further catRAPID analysis revealed a strong RNA-protein interaction between RP11-465L10.10 and myeloid zinc finger gene 1 (MZF1), a transcription factor of MMP9. However, no intense RNA-protein interactions were observed between CTD-2184D3.5 and transcript factors of MAPK6. In conclusions, our study showed differential expression profiles of lncRNAs in TAA and revealed the interaction between certain lncRNAs and coding genes. These data provides insights into new biomarker and therapeutic targets for TAA.

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Section: Discussionmentioning

confidence: 99%

Microarray expression profile analysis of long non‐coding RNAs in thoracic aortic aneurysm

Yang¹,

Yang

2017

The Kaohsiung J of Med Scie

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“…This study comprised 59 patients who underwent open AAA repair between September 2009 and December 2011 at the Department of Surgery, Medical University of Vienna, according to our previously described analysis [ 18 ]. We chose patients treated only with simvastatin or who had taken no statins for at least 6 months before the AAA repair and matched them by AAA diameter and age.…”

Section: Methodsmentioning

confidence: 99%

“…They improve endothelial cell function, modify inflammatory response, reduce VSMC proliferation, and attenuate cholesterol accumulation by reducing concentration of low-density lipoprotein (LDL), triglyceride-rich lipoproteins, and nonsteroidal isoprenoid compounds in plasma [ 15 – 17 ]. Our previous reports showed that patients treated with simvastatin had decreased oxidative stress, reduced proinflammatory TNF- α level, changed concentration of matrix metalloproteinase- (MMP-) 2, MMP-9, and tissue inhibitors of MMPs (TIMPs), and attenuated activity of proinflammatory mediators such as NF- κ B and extracellular signal regulated kinases (ERK) 1/2 [ 18 – 20 ]. Furthermore, statins target circulating neutrophil gelatinase-associated lipocalin (NGAL) and MMP-9/NGAL, the biomarkers of cardiovascular diseases [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Simvastatin Treatment Upregulates HO‐1 in Patients with Abdominal Aortic Aneurysm but Independently of Nrf2

Piechota-Polańczyk

Kopacz

Klóska

et al. 2018

Oxidative Medicine and Cellular Longevity

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Heme oxygenase-1 (HO-1), encoded by HMOX1 gene and regulated by Nrf2 transcription factor, is a cytoprotective enzyme. Its deficiency may exacerbate abdominal aortic aneurysm (AAA) development, which is also often associated with hyperlipidemia. Beneficial effects of statins, the broadly used antilipidemic drugs, were attributed to modulation of Nrf2/HO-1 axis. However, the effect of statins on Nrf2/HO-1 pathway in patients with AAA has not been studied yet. We analyzed AAA tissue from patients treated with simvastatin (N = 28) or without statins (N = 14). Simvastatin treatment increased HO-1 protein level in AAA, both in endothelial cells (ECs) and in smooth muscle cells (SMCs), but increased Nrf2 localization was restricted only to vasa vasorum. Nrf2 target genes HMOX1, NQO1, and GCLM expression remained unchanged in AAA. In vitro studies showed that simvastatin raises HO-1 protein level slightly in ECs and to much higher extent in SMCs, which is not related to Nrf2/ARE activation, although HMOX1 expression is upregulated by simvastatin in both cell types. In conclusion, simvastatin-induced modulation of HO-1 level in ECs and SMCs in vitro is not related to Nrf2/ARE activity. Likewise, divergent HO-1 and Nrf2 localization together with stable expression of Nrf2 target genes, including HMOX1, in AAA tissue denotes Nrf2 independency.

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“…To verify the mechanism behind those changes, measurements were taken of the tissue levels of pro-inflammatory IL-6 and IL-17 and of anti-inflammatory IL-10, as well as the TLR4 receptor, which are known to regulate Cav-1 expression (Jones et al, 2001;Weiss et al, 2015). (Piechota-Polanczyk et al, 2015a).…”

Section: Introductionmentioning

confidence: 99%

Lower levels of Caveolin-1 and higher levels of endothelial nitric oxide synthase are observed in abdominal aortic aneurysm patients treated with simvastatin

et al. 2018

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This study was undertaken to verify whether simvastatin modulates Cav-1/eNOS expression, and if this modulation is associated with changes in pro- and anti-inflammatory cytokine and Toll-like receptor 4 (TLR4) level in abdominal aortic aneurysm (AAA). It is a 1:2 case-control study of non-statin (n=12) and simvastatin-treated patients (n=24) who underwent open AAA repair. Simvastatin treatment decreased Cav-1 (p<0.05) and increased eNOS expression (p<0.01) in the AAA wall. These changes might be dose dependent. The changes in Cav-1 and eNOS were associated with a trend towards decreased IL-6 and IL-17 concentration (p>0.05) and increased IL-10 concentration (p=0.055); however, TLR4 expression was unaffected, suggesting that simvastatin influences Cav-1 and eNOS in the AAA wall by other mechanisms. Simvastatin may modulate Cav-1 and eNOS expression in the aneurysmal wall, indicating a potentially beneficial role for statins in AAA patients.

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The Influence of Simvastatin on NGAL, Matrix Metalloproteinases and Their Tissue Inhibitors in Human Intraluminal Thrombus and Abdominal Aortic Aneurysm Tissue

Cited by 23 publications

References 35 publications

Microarray expression profile analysis of long non‐coding RNAs in thoracic aortic aneurysm

Microarray expression profile analysis of long non‐coding RNAs in thoracic aortic aneurysm

Simvastatin Treatment Upregulates HO‐1 in Patients with Abdominal Aortic Aneurysm but Independently of Nrf2

Lower levels of Caveolin-1 and higher levels of endothelial nitric oxide synthase are observed in abdominal aortic aneurysm patients treated with simvastatin

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