Glycocalyx in Atherosclerosis-Relevant Endothelium Function and as a Therapeutic Target.
Glycocalyx in Atherosclerosis-Relevant Endothelium Function and as a Therapeutic Target.
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DOI：
10.1007/s11883-017-0691-9
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发表时间：
2017-11-10
影响因子：
5.8
通讯作者：
Ebong EE
中科院分区：
文献类型：
--
作者：
Mitra R;O'Neil GL;Harding IC;Cheng MJ;Mensah SA;Ebong EE
细胞表面附着的细胞外糖萼（GCX）层是内皮细胞（EC）功能和EC依赖性血管健康的主要贡献者，并且是对抗血管疾病（包括动脉粥样硬化）的第一道防线。在这里，我们强调我们的研究结果，关于三个GCX依赖EC功能，这是改变时，GCX脱落和动脉粥样硬化。我们讨论了为什么GCX是预防和治疗动脉粥样硬化的可行选择。GCX调节EC活动，如屏障和过滤功能，活跃的细胞间通讯和血管张力调节，有助于整个血管壁的功能。Atheroprone血管区域，包括分叉部位，在GCX中表现出破裂。这种GCX降解允许增加脂质通量，从而促进血管壁中的脂质沉积，这是动脉粥样硬化的标志。GCX降解还改变了EC与EC的通讯，同时增加了EC与炎症细胞的相互作用，使炎症细胞能够迁移到血管壁中。具体地说，炎性巨噬细胞和泡沫细胞出现在动脉粥样硬化的早期阶段。此外，GCX降解通过引起EC降低其产生血管扩张剂一氧化氮的内皮一氧化氮合酶（eNOS）的表达来解除血管张力。血管舒张的丧失支持血管收缩，这促进动脉粥样硬化的进展。常见的动脉粥样硬化药物治疗包括降脂和抗血小板治疗。这些治疗方法都没有专门针对内皮GCX，尽管GCX是动脉粥样硬化斗争的前线。这篇综述证明了靶向GCX治疗的可行性，以支持适当的EC功能和预防和/或治疗动脉粥样硬化。
The cell surface-attached extracellular glycocalyx (GCX) layer is a major contributor to endothelial cell (EC) function and EC-dependent vascular health and is a first line of defense against vascular diseases including atherosclerosis. Here, we highlight our findings regarding three GCX-dependent EC functions, which are altered when GCX is shed and in atherosclerosis. We discuss why the GCX is a viable option for the prevention and treatment of atherosclerosis. GCX regulated EC activities such as barrier and filtration function, active cell-to-cell communication, and vascular tone mediation contribute to function of the entire vascular wall. Atheroprone vessel regions, including bifurcation sites, exhibit breakdown in GCX. This GCX degradation allows increased lipid flux and thereby promotes lipid deposition in the vessel walls, a hallmark of atherosclerosis. GCX degradation also alters EC-to-EC communication while increasing EC-to-inflammatory cell interactions that enable inflammatory cells to migrate into the vessel wall. Inflammatory macrophages and foam cells, to be specific, appear in early stages of atherosclerosis. Furthermore, GCX degradation deregulates vascular tone, by causing ECs to reduce their expression of endothelial nitric oxide synthase (eNOS) which produces the vasodilator, nitric oxide. Loss of vasodilation supports vasoconstriction, which promotes the progression of atherosclerosis. Common medicinal atherosclerosis therapies include lipid lowering and anti-platelet therapies. None of these treatments specifically target the endothelial GCX, although the GCX is at the front-line in atherosclerosis combat. This review demonstrates the viability of targeting the GCX therapeutically, to support proper EC functionality and prevent and/or treat atherosclerosis.
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影响因子：
3.7
作者：
Chen C;Khismatullin DB
通讯作者：
Khismatullin DB
DOI：
10.1039/c3ib40199e
发表时间：
2014-03
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Ebong EE;Lopez-Quintero SV;Rizzo V;Spray DC;Tarbell JM
通讯作者：
Tarbell JM
DOI：
10.1152/ajpheart.00204.2005
发表时间：
2006-05-01
影响因子：
4.8
作者：
Ebong, EE;Kim, S;DePaola, N
通讯作者：
DePaola, N
影响因子：
5.3
作者：
Cancel, Limary M.;Ebong, Eno E.;Mensah, Solomon;Hirschberg, Carly;Tarbell, John M.
通讯作者：
Tarbell, John M.
影响因子：
33.6
作者：
Chiu JJ;Chien S
通讯作者：
Chien S