Department of Vascular Surgery and Angiology, Pomeranian Medical University, Szczecin, Poland.
Department of Forensic Medicine, Pomeranian Medical University, Szczecin, Poland.
FASEB J. 2019 Jan;33(1):885-895. doi: 10.1096/fj.201800633R. Epub 2018 Oct 23.
The possibility that oxidative stress promotes degradation of the extracellular matrix and a relationship between intraluminal thrombus (ILT) thickness and proteolytic activity within the abdominal aortic aneurysm (AAA) wall has been suggested. In the present study, the hypothesis that thin ILT is correlated with an increase in oxidative stress-related enzymes and matrix metalloproteinase-9 (MMP-9) expression within the human AAA wall was investigated. We also studied the antioxidant activity of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase, and thioredoxin within the full-thickness AAA wall and through fluoroimmunohistochemical staining of catalase and MMP-9 expression within the inner and outer media, in relation to ILT thickness. Reactive oxygen species control the degradation and remodeling of the extracellular matrix by up-regulating proteolytic enzymes, such as MMPs. Results showed that oxidative stress and proteolytic enzyme expression were simultaneously, significantly higher within thin thrombus (≤10 mm)-covered aneurysm wall when compared with the wall covered by thick thrombus (≥25 mm). These findings provide the first demonstration, to our knowledge, of a causative link between oxidative stress instigating proteolytic enzyme expression at the tissue level and human AAA development. Presence of a thin circumferential thrombus should always be considered as a risk factor for the greatest increase in aneurysm growth rate and rupture, giving an indication for surgery timing.-Wiernicki, I., Parafiniuk, M., Kolasa-Wołosiuk, A., Gutowska, I., Kazimierczak, A., Clark, J., Baranowska-Bosiacka, I., Szumilowicz, P., Gutowski, P. Relationship between aortic wall oxidative stress/proteolytic enzyme expression and intraluminal thrombus thickness indicates a novel pathomechanism in the progression of human abdominal aortic aneurysm.
氧化应激促进细胞外基质降解的可能性，以及腹主动脉瘤（AAA）壁内管腔内血栓（ILT）厚度与蛋白水解活性之间的关系已经被提出。在本研究中，假设薄的 ILT 与 AAA 壁内与氧化应激相关的酶和基质金属蛋白酶-9（MMP-9）表达的增加相关，这一假说得到了研究。我们还研究了全厚度 AAA 壁内超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和硫氧还蛋白的抗氧化活性，并通过对内外膜内过氧化氢酶和 MMP-9 表达的荧光免疫组织化学染色，研究了与 ILT 厚度的关系。活性氧通过上调蛋白水解酶，如 MMPs，来控制细胞外基质的降解和重塑。结果表明，与厚血栓（≥25 毫米）覆盖的动脉瘤壁相比，薄血栓（≤10 毫米）覆盖的动脉瘤壁中的氧化应激和蛋白水解酶表达同时显著升高。这些发现首次提供了一个因果关系的证据，即在组织水平上，氧化应激引发蛋白水解酶表达与人类 AAA 的发展之间存在因果关系。存在环形薄血栓应始终被视为动脉瘤生长速度和破裂增加的最大风险因素，提示手术时机。-Wiernicki, I., Parafiniuk, M., Kolasa-Wołosiuk, A., Gutowska, I., Kazimierczak, A., Clark, J., Baranowska-Bosiacka, I., Szumilowicz, P., Gutowski, P. 主动脉壁氧化应激/蛋白水解酶表达与管腔内血栓厚度的关系表明，在人类腹主动脉瘤进展的新病理机制。
