Endothelial glycocalyx sensitivity to chemical and mechanical sub-endothelial substrate properties.
Endothelial glycocalyx sensitivity to chemical and mechanical sub-endothelial substrate properties.
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DOI：
10.3389/fbioe.2023.1250348
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发表时间：
2023
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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作者：
Glyocalyx(GCX)是一种富含碳水化合物的结构，包裹在内皮细胞(ECs)的表面，并排列在血管腔内。血管环境中的机械扰动，如血管僵硬，可以通过机械传感器(如GCX)传递并发送到内皮细胞。不利的僵直改变了GCX介导的机械转导，并导致EC功能障碍，最终导致动脉粥样硬化性心血管疾病。为了理解GCX调节的机械转导事件，需要一个模拟体内血管条件的体外模型。为此，我们研究了基质的化学和机械性质对GCX表达的影响，方法是制备一种基于胶原源多肽明胶的可调性不肿胀基质。为了研究基质组成的影响，我们进行了不同浓度(60-25,000μg/mL)的明胶和明胶甲基丙烯酸酯(GelMA)与纤维连接蛋白(60μg/mL)的比较分析，纤维连接蛋白是GCX相关研究的标准包衣材料。通过免疫细胞化学分析，我们首次表明不同底物组成和浓度改变了人脐静脉内皮细胞(HUVECs)上GCX的总体表达。随后，制备了硬度为2.5和5 kpa的GelMA水凝胶，代表健康的血管组织，以及对应于患病的血管组织的10 kpa的硬度。免疫细胞化学分析显示，在不同硬度水平的水凝胶中，HUVECs中GCX的表达没有变化，但其主要多糖组分表现出不同模式的失调。例如，病理底物上硫酸乙酰肝素的表达显著减少(10kpa)，而唾液酸的表达随着基质硬度的增加而增加。本研究提示GCX在健康和患病基质的不同化学和机械条件下影响内皮细胞调节屏障功能、免疫细胞黏附和机械转导功能的具体机制。
Glycocalyx (GCX) is a carbohydrate-rich structure that coats the surface of endothelial cells (ECs) and lines the blood vessel lumen. Mechanical perturbations in the vascular environment, such as blood vessel stiffness, can be transduced and sent to ECs through mechanosensors such as GCX. Adverse stiffness alters GCX-mediated mechanotransduction and leads to EC dysfunction and eventually atherosclerotic cardiovascular diseases. To understand GCX-regulated mechanotransduction events, an in vitro model emulating in vivo vessel conditions is needed. To this end, we investigated the impact of matrix chemical and mechanical properties on GCX expression via fabricating a tunable non-swelling matrix based on the collagen-derived polypeptide, gelatin. To study the effect of matrix composition, we conducted a comparative analysis of GCX expression using different concentrations (60–25,000 μg/mL) of gelatin and gelatin methacrylate (GelMA) in comparison to fibronectin (60 μg/mL), a standard coating material for GCX-related studies. Using immunocytochemistry analysis, we showed for the first time that different substrate compositions and concentrations altered the overall GCX expression on human umbilical vein ECs (HUVECs). Subsequently, GelMA hydrogels were fabricated with stiffnesses of 2.5 and 5 kPa, representing healthy vessel tissues, and 10 kPa, corresponding to diseased vessel tissues. Immunocytochemistry analysis showed that on hydrogels with different levels of stiffness, the GCX expression in HUVECs remained unchanged, while its major polysaccharide components exhibited dysregulation in distinct patterns. For example, there was a significant decrease in heparan sulfate expression on pathological substrates (10 kPa), while sialic acid expression increased with increased matrix stiffness. This study suggests the specific mechanisms through which GCX may influence ECs in modulating barrier function, immune cell adhesion, and mechanotransduction function under distinct chemical and mechanical conditions of both healthy and diseased substrates.
使用纤连蛋白附着蛋白衍生的肽 - 脂聚合物结合物膀胱肿瘤细胞对脂质体的靶向和内在化。
影响因子：
4.7
作者：
Lee Y;Kischuk E;Crist S;Ratliff TL;Thompson DH
通讯作者：
Thompson DH
DOI：
10.1083/jcb.30.3.660
发表时间：
1966-09
期刊：
The Journal of cell biology
影响因子：
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作者：
Wallach DF;Kamat VB
通讯作者：
Kamat VB