Wang Nan, Vendrov Kimberly C, Simmons Brian P, Schuck Robert N, Stouffer George A, Lee Craig R
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Division of Cardiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Prostaglandins Other Lipid Mediat. 2018 Jan;134:24-31. doi: 10.1016/j.prostaglandins.2017.11.003. Epub 2017 Nov 16.
Cyclooxygenase-derived thromboxane (TxA2) and prostacyclin (PGI2) regulate atherogenesis in preclinical models. However, the relationship between TxA2 and PGI2 biosynthesis, vascular inflammation, and atherosclerotic cardiovascular disease (ASCVD) progression in humans remains unclear. The association between stable urine metabolites of thromboxane (TxA2-M) and prostacyclin (PGI2-M), circulating levels of cellular adhesion molecules (CAMs: E-selectin, P-selectin), chemokines and C-reactive protein, and the incidence of major adverse cardiovascular events (MACE) were evaluated in 120 patients with stable ASCVD on aspirin therapy. Urinary TxA2-M levels were significantly correlated with circulating P-selectin (r=0.319, p<0.001) and E-selectin (r=0.245, p=0.007) levels, and associated with higher risk of MACE (p=0.043). In contrast, PGI2-M levels were not significantly associated with CAM levels or MACE. These results provide insight into the contribution of TxA2 biosynthesis to ASCVD progression in humans, and suggest that patients with elevated TxA2-M levels may be predisposed to advanced platelet and endothelial activation and higher risk of adverse cardiovascular outcomes.
环氧化酶衍生的血栓素（TxA2）和前列环素（PGI2）在临床前模型中调节动脉粥样硬化的发生。然而，在人类中，TxA2与PGI2生物合成、血管炎症和动脉粥样硬化性心血管疾病（ASCVD）进展之间的关系仍不清楚。我们评估了120例接受阿司匹林治疗的稳定ASCVD患者中，血栓素（TxA2-M）和前列环素（PGI2-M）的稳定尿液代谢产物、细胞黏附分子（CAMs：E-选择素、P-选择素）的循环水平、趋化因子和C反应蛋白与主要不良心血管事件（MACE）发生率之间的关联。尿TxA2-M水平与循环P-选择素（r=0.319，p<0.001）和E-选择素（r=0.245，p=0.007）水平显著相关，并与MACE风险较高相关（p=0.043）。相比之下，PGI2-M水平与CAM水平或MACE无显著关联。这些结果为TxA2生物合成对人类ASCVD进展的作用提供了见解，并表明TxA2-M水平升高的患者可能易发生晚期血小板和内皮细胞激活以及不良心血管结局风险较高。
