Screening Analysis of Proteolytic Enzymes and Their Inhibitors in the Leaflets of Epoxy-Treated Bioprosthetic Heart Valves Explanted due to Dysfunction

IF 0.4 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2022-08-15 DOI:10.1134/S1990750822030076

A. E. Kostyunin, T. V. Glushkova, D. K. Shishkova, V. E. Markova, E. A. Ovcharenko

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引用次数: 1

Abstract—

Bioprosthetic heart valves (BHVs) have lower thrombogenicity rates and excellent hemodynamic parameters similar to native valves. However, the lifespan of these medical devices is limited to 15 years due to the structural valve degeneration (SVD). One of the mechanisms underlying functional impairment and calcification of BHVs includes proteolytic degradation of biomaterials. However, proteases found in xenogeneic tissue of BHVs remain poorly studied. In this study using the dot blot assay, we have performed a screening analysis of proteolytic enzymes and their inhibitors in the leaflets of five BHVs explanted due to dysfunction. Five aortic valves (AVs) explanted due to calcific aortic valve disease were used as a comparison group. The results of the study have demonstrated the presence of at least 17 proteases and 19 of their inhibitors in BHVs. In the AVs 20 proteases and 21 of their inhibitors were identified. Small quantitative differences were found between proteomic profiles of BHVs and AVs. Matrix metalloproteinases (MMPs) were expressed in BHVs and AVs at comparable levels, but the level of tissue inhibitors of metalloproteinases-1/-2 and reversion-inducing-cysteine-rich protein with Kazal motifs in implant tissues was lower than in native valves. This suggests that excessive activity of MMPs cannot be counterbalanced by their specific inhibitors in BHVs and therefore MMPs initiate the process of degeneration. Moreover, the detection of a wide range of proteolytic enzymes and their inhibitors in the degenerated BHVs suggests the existence of several pathophysiological pathways that can lead to SVD.

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环氧树脂处理的功能障碍外植心脏瓣膜小叶蛋白水解酶及其抑制剂的筛选分析

生物人工心脏瓣膜(bhv)具有较低的血栓形成率和良好的血流动力学参数，与天然瓣膜相似。然而，由于结构性瓣膜退行性变(SVD)，这些医疗器械的使用寿命被限制在15年。bhv功能损伤和钙化的机制之一包括生物材料的蛋白水解降解。然而，在bhv异种组织中发现的蛋白酶研究仍然很少。在这项研究中，我们使用点印迹法对5个因功能障碍而外植的bhv小叶中的蛋白水解酶及其抑制剂进行了筛选分析。以5例因钙化性主动脉瓣病变而切除的主动脉瓣(AVs)为对照组。研究结果表明，bhv中存在至少17种蛋白酶和19种蛋白酶抑制剂。在av中鉴定出20种蛋白酶和21种蛋白酶抑制剂。在bhv和av的蛋白质组学谱之间发现了微小的数量差异。基质金属蛋白酶(MMPs)在bhv和AVs中的表达水平相当，但金属蛋白酶组织抑制剂-1/ 2和具有Kazal基序的逆转诱导半胱氨酸富蛋白在植入组织中的表达水平低于天然瓣膜。这表明MMPs的过度活性不能被bhv中的特定抑制剂抵消，因此MMPs启动了变性过程。此外，在退行性bhv中检测到广泛的蛋白水解酶及其抑制剂，表明存在几种可导致SVD的病理生理途径。

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Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

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1.10

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期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.