Diosmin and its glycocalyx restorative and anti-inflammatory effects on injured blood vessels.
Diosmin and its glycocalyx restorative and anti-inflammatory effects on injured blood vessels.
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地奥司明及其糖萼对受损血管的恢复和抗炎作用。
DOI：
10.1096/fj.202200053rr
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Ebong,EnoE
中科院分区：
文献类型：
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作者：
Mitra,Ronodeep;Nersesyan,Alina;Pentland,Kaleigh;Melin,MMark;Levy,RobertM;Ebong,EnoE
内皮是一个重要的自我平衡器官，调节血管的通透性和张力。在生理条件下，内皮刺激诱导血管扩张剂内皮一氧化氮（eNO）释放，并阻止粘附分子的可及性和白细胞粘附和迁移到血管壁。内皮功能障碍是心血管疾病包括动脉粥样硬化的主要事件。很少注意到一个重要的内皮细胞结构，内皮糖萼（GCX），一个带负电荷的异质多糖，作为一个保护性覆盖内皮细胞，使内皮细胞能够将机械刺激转化为各种生物和化学活性。因此，内皮GCX脱落在内皮功能障碍中起作用，例如通过增加血管通透性和降低血管张力。因此，人们越来越关注开发专注于GCX修复的疗法，以限制下游内皮功能障碍并预防进一步的下游心血管事件。在这里，我们介绍了地奥司明（3′，5，7-三羟基-4 ′-甲氧基黄酮-7-鼠李糖葡萄糖苷），地奥司汀的黄酮苷，其下调粘附分子表达，降低炎症和毛细血管通透性，并上调eNO表达。由于地奥司明对血管系统的这些多效性作用，一种可能的未确定的作用机制是通过GCX恢复。我们假设地奥司明积极影响GCX完整性沿着GCX相关内皮功能。我们的假设在部分结扎左颈动脉（LCA）小鼠模型中进行了测试，其中右颈动脉是每只小鼠的对照。地奥司明（50 mg/kg）每天给药7天，结扎后72 h。在结扎的小鼠LCA内，地奥司明治疗升高了活化的eNO合酶水平，抑制了炎性细胞摄取，降低了血管壁厚度，增加了血管直径，并增加了血管壁的GCX覆盖。ELISA显示地奥司明给药小鼠血浆样品中透明质酸浓度降低，表明GCX脱落减少。总之，地奥司明支持内皮GCX的完整性，我们将地奥司明对内皮功能的保护归因于炎症因子表达减弱和血管张力恢复。
The endothelium, a crucial homeostatic organ, regulates vascular permeability and tone. Under physiological conditions, endothelial stimulation induces vasodilator endothelial nitric oxide (eNO) release and prevents adhesion molecule accessibility and leukocyte adhesion and migration into vessel walls. Endothelium dysfunction is a principal event in cardiovascular disorders, including atherosclerosis. Minimal attention is given to an important endothelial cell structure, the endothelial glycocalyx (GCX), a negatively charged heterogeneous polysaccharide that serves as a protective covering for endothelial cells and enables endothelial cells to transduce mechanical stimuli into various biological and chemical activities. Endothelial GCX shedding thus plays a role in endothelial dysfunction, for example by increasing vascular permeability and decreasing vessel tone. Consequently, there is increasing interest in developing therapies that focus on GCX repair to limit downstream endothelium dysfunction and prevent further downstream cardiovascular events. Here, we present diosmin (3′,5,7‐trihydroxy‐4′‐methoxyflavone‐7‐rhamnoglucoside), a flavone glycoside of diosmetin, which downregulates adhesive molecule expression, decreases inflammation and capillary permeability, and upregulates eNO expression. Due to these pleiotropic effects of diosmin on the vasculature, a possible unidentified mechanism of action is through GCX restoration. We hypothesize that diosmin positively affects GCX integrity along with GCX‐related endothelial functions. Our hypothesis was tested in a partial ligation left carotid artery (LCA) mouse model, where the right carotid artery was the control for each mouse. Diosmin (50 mg/kg) was administered daily for 7 days, 72 h after ligation. Within the ligated mice LCAs, diosmin treatment elevated the activated eNO synthase level, inhibited inflammatory cell uptake, decreased vessel wall thickness, increased vessel diameter, and increased GCX coverage of the vessel wall. ELISA showed a decrease in hyaluronan concentration in plasma samples of diosmin‐treated mice, signifying reduced GCX shedding. In summary, diosmin supported endothelial GCX integrity, to which we attribute diosmin's preservation of endothelial function as indicated by attenuated expression of inflammatory factors and restored vascular tone.