a School of Pharmacy, University of Camerino , Camerino , Italy .
b School of Bioscience and Veterinary Medicine, University of Camerino , Camerino , Italy, and.
Clin Exp Hypertens. 2016;38(1):30-8. doi: 10.3109/10641963.2015.1047950. Epub 2015 Jul 24.
Endothelial cells represent an important vascular site of signaling and development of damage during ischemia, inflammation and other pathological conditions. Excessive reactive oxygen species production causes pathological activation of endothelium including exposure of cell to adhesion molecules. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are members of the immunoglobulin super-family which are present on the surface of endothelial cells. These molecules represent important markers of endothelial inflammation. The present study was designed to investigate, with immunochemical and immunohistochemical techniques, the effect of treatment with (+/-)-alpha lipoic (thioctic) acid and its enantiomers on heart and kidney endothelium in spontaneously hypertensive rats (SHR). Arterial hypertension is accompanied by an increased oxidative stress status in the heart characterized by thiobarbituric acid reactive substances (TBARS) and nucleic acid oxidation increase. The higher oxidative stress also modifies adhesion molecules expression. In the heart VCAM-1, which was higher than ICAM-1 and PECAM-1, was increased in SHR. ICAM-1, VCAM-1 and PECAM-1 expression was significantly greater in the renal endothelium of SHR. (+/-)-Alpha lipoic acid and (+)-alpha lipoic acid treatment significantly decreased TBARS levels, the nucleic acid oxidation and prevented adhesion molecules expression in cardiac and renal vascular endothelium. These data suggest that endothelial molecules may be used for studying the mechanisms of vascular injury on target organs of hypertension. The effects observed after treatment with (+)-alpha lipoic acid could open new perspectives for countering heart and kidney microvascular injury which represent a common feature in hypertensive end-organs damage.
内皮细胞是信号转导和缺血、炎症和其他病理状态下损伤发生的重要血管部位。过量的活性氧产生导致内皮细胞的病理性激活，包括细胞暴露于粘附分子。细胞间粘附分子-1（ICAM-1）、血管细胞粘附分子-1（VCAM-1）和血小板内皮细胞粘附分子-1（PECAM-1）是免疫球蛋白超家族的成员，存在于内皮细胞表面。这些分子是内皮炎症的重要标志物。本研究旨在采用免疫化学和免疫组织化学技术，研究（±）-α-硫辛酸（硫辛酸）及其对映异构体对自发性高血压大鼠（SHR）心脏和肾脏内皮的治疗作用。动脉高血压伴有心脏氧化应激状态增加，表现为硫代巴比妥酸反应物质（TBARS）和核酸氧化增加。更高的氧化应激也改变了粘附分子的表达。在心脏中，VCAM-1 高于 ICAM-1 和 PECAM-1，在 SHR 中增加。SHR 肾脏内皮中 ICAM-1、VCAM-1 和 PECAM-1 的表达显著增加。（±）-α-硫辛酸和（+）-α-硫辛酸治疗显著降低了心脏和肾脏血管内皮中的 TBARS 水平、核酸氧化，并防止了粘附分子的表达。这些数据表明，内皮分子可用于研究高血压靶器官血管损伤的机制。用（+）-α-硫辛酸治疗后观察到的效果可能为对抗心脏和肾脏微血管损伤开辟新的前景，这是高血压靶器官损伤的共同特征。
