Atherogenic diet-diminished endothelial glycocalyx contributes to impaired vasomotor properties in rat
Atherogenic diet-diminished endothelial glycocalyx contributes to impaired vasomotor properties in rat
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致动脉粥样硬化饮食减少的内皮糖萼导致大鼠血管舒缩特性受损
DOI：
10.1152/ajpheart.00039.2020
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Deng Xiaoyan
中科院分区：
文献类型：
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作者：
Kang Hongyan;Sun Anqiang;Wu Qiuhong;Yang Jiali;Zhang Weichen;Qu Yuxin;Gao Menghan;Deng Xiaoyan
高胆固醇血症和动脉粥样硬化引起的血管功能障碍可能参与动脉粥样硬化的许多临床表现，包括心绞痛、急性心肌梗死和心源性猝死。然而，其内在机制尚不清楚。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的机械传感器。在本研究中，我们通过共聚焦显微镜证实，与正常饮食（NC）相比，喂食12周高胆固醇饮食（HC）的SD雄性大鼠的颈总动脉和颈总动脉的内皮糖萼尺寸显著减小，（分别为2.89 ± 0.41 μm和3.25 ± 0.44 μm）和内窦区（分别为2.35 ± 0.07 μm和3.46 ± 0.86 μm）。此外，我们通过实时PCR表明，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）相关基因的显著下调，包括syndecan-3，磷脂酰肌醇蛋白聚糖-1和EXT 1，而不是由于硫酸化糖胺聚糖（sGAG）从血管壁向血浆的脱落增强。同时，颈总动脉对去甲肾上腺素（NE）和乙酰胆碱（ACh）反应的平均收缩力和舒张力分别降低约0.34倍和0.13倍，同时伴有较低水平的一氧化氮（NO）释放。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，从而导致血管舒缩特性受损。新&值得注意的是，十二周高胆固醇（HC）饮食减少了Sprague-Dawley（SD）雄性大鼠内皮糖萼的厚度，这主要归因于硫酸乙酰肝素蛋白聚糖相关基因的下调（多配体蛋白聚糖-3，磷脂酰肌醇蛋白聚糖-1，EXT 1），不是由硫酸化糖胺聚糖（sGAG）向血浆中的增强脱落引起的。HC减少的糖萼可能会干扰其局部剪切应力的机械转导，降低一氧化氮（NO）的释放，并损害血管对去甲肾上腺素（NE）和乙酰胆碱（ACh）的反应。
Hypercholesterolemia- and atherosclerosis-caused vasomotor property 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 in Sprague-Dawley (SD) male rats fed a 12-wk high-cholesterol diet (HC) compared with the normal diet (NC) 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). Furthermore, we showed by real-time PCR that this dimension modification of endothelial glycocalyx may be attributed to a significant downregulation of heparan sulfate proteoglycan (HSPG)-related genes, including syndecan-3, glypican-1, and EXT1, not resulting from an enhanced shedding of sulfated glycosaminoglycans (sGAGs) 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 ~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.NEW & NOTEWORTHYTwelve-week high-cholesterol (HC) diet reduces the thickness of the endothelial glycocalyx in Sprague-Dawley (SD) male rats, which is mainly attributed to a downregulation of heparan sulfate proteoglycan-related genes (syndecan-3, glypican-1, EXT1), not resulting from an enhanced shedding of sulfated glycosaminoglycans (sGAGs) into the plasma. HC-diminished glycocalyx may disturb its mechanotransduction of local shear stress, lower nitric oxide (NO) release, and impair vasomotor responses to norepinephrine (NE) and acetylcholine (ACh).