Hypercholesterolemia and atherosclerosis caused vasomotor properties dysfunction may be involved in many clinic manifestations of atherosclerosis, including angina, acute myocardial infarction, and sudden cardiac death. However, its underlying mechanism is not clear. The endothelial glycocalyx is a protective surface layer on the endothelial cells, serving as a molecular sieve, cell adhesion modulator, and mechanosensor for blood flow. In the present study, we demonstrated by confocal microscopy that the dimension of the endothelial glycocalyx reduced significantly in both the common carotid artery (2.89±0.41 µm and 3.25±0.44 μm, respectively) and the internal sinus region (2.35±0.07 µm and 3.46±0.86 μm, respectively) of the 12 week high cholesterol fed SD male rats (HC) as compared to the normal diet (NC). Furthermore, we showed by real time PCR that this dimension modification of endothelial glycocalyx may be attributed to a significant down-regulation of heparan sulfate proteoglycans (HSPG) related genes, including syndecan-3, glypican-1, and EXT1, not resulting from an enhanced shedding of sulfated glycosaminoglycans (sGAG) from the vessel wall to the plasma. Meanwhile, the mean contraction and relaxation forces of the common carotid artery with responses to norepinephrine (Ne) and acetylcholine (ACh) decreased approximately to 0.34 and 0.13 fold, respectively, accompanied by a lower level of nitric oxide (NO) release. These findings suggest that the atherogenic high cholesterol diet diminished endothelial glycocalyx and disturbed the local NO release, thus contributing to the impaired vasomotor properties of the vessel.

中文翻译：

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降低饮食致动脉粥样硬化的内皮糖萼可导致大鼠血管舒缩功能受损。

高胆固醇血症和动脉粥样硬化引起的血管舒缩功能障碍可能与动脉粥样硬化的许多临床表现有关，包括心绞痛，急性心肌梗塞和心源性猝死。但是，其潜在机制尚不清楚。内皮糖萼是内皮细胞上的保护性表面层，用作分子筛，细胞粘附调节剂和血流机械传感器。在本研究中，我们通过共聚焦显微镜证明，在颈总动脉（分别为2.89±0.41 µm和3.25±0.44μm）和内窦区域（2.35±0.07 µm和3.46）中，内皮糖萼的尺寸均显着减小。与正常饮食（NC）相比，饲喂12周高胆固醇的SD雄性大鼠（HC）分别为±0.86μm。此外，我们通过实时PCR显示，内皮糖萼的这种尺寸修饰可能归因于硫酸乙酰肝素蛋白聚糖（HSPG）相关基因的显着下调，包括syndecan-3，glypican-1和EXT1，而不是由脱落增加引起的从血管壁到血浆的硫酸化糖胺聚糖（sGAG）。同时，响应去甲肾上腺素（Ne）和乙酰胆碱（ACh）的反应，颈总动脉的平均收缩力和舒张力分别降低至约0.34和0.13倍，同时一氧化氮（NO）释放水平较低。这些发现表明，致动脉粥样硬化的高胆固醇饮食减少了内皮糖萼并扰乱了局部NO的释放，从而导致血管血管舒缩特性受损。