Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins.
Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins.
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DOI：
10.1093/cvr/cvw075
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发表时间：
2016-06-01
影响因子：
10.8
通讯作者：
Mayr M
中科院分区：
文献类型：
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作者：
Barallobre-Barreiro J;Oklu R;Lynch M;Fava M;Baig F;Yin X;Barwari T;Potier DN;Albadawi H;Jahangiri M;Porter KE;Watkins MT;Misra S;Stoughton J;Mayr M
细胞外基质重塑与许多血管疾病有关，包括静脉高压和静脉曲张。然而，到目前为止，还没有系统的分析基质重塑人静脉。为了了解静脉高压的后果，使用靶向细胞外基质的蛋白质组学方法评估了正常和静脉曲张。收集静脉切除术中取出的曲张大隐静脉和冠状动脉搭桥术中获得的正常大隐静脉进行蛋白质组学分析。细胞外基质蛋白从静脉组织中富集。蛋白质组学分析显示存在>150种细胞外基质蛋白，其中48种以前在静脉组织中未检测到。曲张静脉中细胞外基质重塑的特征是聚集蛋白聚糖和几种富含亮氨酸的小蛋白聚糖的丢失以及I型胶原和层粘连蛋白的代偿性增加。相同组织的基因表达分析表明，与静脉高压相关的重塑过程主要发生在蛋白质而不是转录水平。在静脉曲张中聚集蛋白聚糖的丢失被聚集蛋白聚糖酶表达的减少所抵消。类糜蛋白酶和类胰蛋白酶β1是上调的蛋白酶。这些丝氨酸蛋白酶对静脉细胞外基质的作用通过用重组酶孵育正常隐静脉来进一步探索。蛋白质组学分析表明，广泛的细胞外基质降解后，类胰蛋白酶β1消化。相比之下，糜酶是不太有力的，主要降解基膜相关蛋白。目前的蛋白质组学研究提供了前所未有的见解的表达和血管细胞外基质的结构和调节成分在静脉曲张的降解。
Extracellular matrix remodelling has been implicated in a number of vascular conditions, including venous hypertension and varicose veins. However, to date, no systematic analysis of matrix remodelling in human veins has been performed. To understand the consequences of venous hypertension, normal and varicose veins were evaluated using proteomics approaches targeting the extracellular matrix. Varicose saphenous veins removed during phlebectomy and normal saphenous veins obtained during coronary artery bypass surgery were collected for proteomics analysis. Extracellular matrix proteins were enriched from venous tissues. The proteomics analysis revealed the presence of >150 extracellular matrix proteins, of which 48 had not been previously detected in venous tissue. Extracellular matrix remodelling in varicose veins was characterized by a loss of aggrecan and several small leucine-rich proteoglycans and a compensatory increase in collagen I and laminins. Gene expression analysis of the same tissues suggested that the remodelling process associated with venous hypertension predominantly occurs at the protein rather than the transcript level. The loss of aggrecan in varicose veins was paralleled by a reduced expression of aggrecanases. Chymase and tryptase β1 were among the up-regulated proteases. The effect of these serine proteases on the venous extracellular matrix was further explored by incubating normal saphenous veins with recombinant enzymes. Proteomics analysis revealed extensive extracellular matrix degradation after digestion with tryptase β1. In comparison, chymase was less potent and degraded predominantly basement membrane-associated proteins. The present proteomics study provides unprecedented insights into the expression and degradation of structural and regulatory components of the vascular extracellular matrix in varicosis.