Degenerative aortic valve disease and diabetes: Implications for a link between proteoglycans and diabetic disorders in the aortic valve
Degenerative aortic valve disease and diabetes: Implications for a link between proteoglycans and diabetic disorders in the aortic valve
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DOI：
10.1177/1479164118817922
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发表时间：
2019-05-01
影响因子：
2.4
通讯作者：
Lichtenberg, Artur
中科院分区：
文献类型：
--
作者：
Barth, Mareike;Selig, Jessica I.;Lichtenberg, Artur
退行性主动脉瓣疾病合并糖尿病在世界范围内是一个日益沉重的负担。越来越多的证据表明，尤其是富含亮氨酸的小分子蛋白多糖与退行性主动脉瓣疾病的发生有关。然而，这些分子在糖尿病病程中的作用还没有被详细阐明，以前的研究仍然存在争议。因此，本研究的目的是扩大对富含亮氨酸的小分子蛋白多糖在退行性主动脉瓣疾病中的认识，并检测糖尿病和高血糖对主动脉瓣和瓣膜间质细胞的影响。采用逆转录聚合酶链式反应、Western印迹、酶联免疫吸附试验、免疫组织学和比色法进行分析。我们可以证明Biglycan，而不是Decorin和Lumcan，在退变的人主动脉瓣尖端表达上调。亚群分析表明，Biglycan的上调是阶段依赖的。在体内，双聚糖的丢失会导致分期依赖性的钙化，也会对细胞外基质中的间质细胞产生迁移效应。在退行性主动脉瓣病变的晚期，糖尿病增加了主动脉瓣中Biglycan的表达。在体外，高血糖和促退变条件的结合导致了双聚糖的上调。总而言之，Biglycan代表了退行性主动脉瓣疾病和糖尿病之间的潜在联系。
Degenerative aortic valve disease in combination with diabetes is an increasing burden worldwide. There is growing evidence that particularly small leucine-rich proteoglycans are involved in the development of degenerative aortic valve disease. Nevertheless, the role of these molecules in this disease in the course of diabetes has not been elucidated in detail and previous studies remain controversial. Therefore, the aim of this study is to broaden the knowledge about small leucine-rich proteoglycans in degenerative aortic valve disease and the influence of diabetes and hyperglycaemia on aortic valves and valvular interstitial cells is examined. Analyses were performed using reverse-transcription polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, (immuno)histology and colorimetric assays. We could show that biglycan, but not decorin and lumican, is upregulated in degenerated human aortic valve cusps. Subgroup analysis reveals that upregulation of biglycan is stage-dependent. In vivo, loss of biglycan leads to stage-dependent calcification and also to migratory effects on interstitial cells within the extracellular matrix. In late stages of degenerative aortic valve disease, diabetes increases the expression of biglycan in aortic valves. In vitro, the combinations of hyperglycaemic with pro-degenerative conditions lead to an upregulation of biglycan. In conclusion, biglycan represents a potential link between degenerative aortic valve disease and diabetes.