Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
Mediterranea Cardiocentro-Napoli, Naples, Italy.
Br J Pharmacol. 2021 May;178(10):2146-2159. doi: 10.1111/bph.15399. Epub 2021 Apr 24.
Oxidative stress and insufficient autophagy activity are associated with inflammatory processes and are common features of many cardiovascular diseases (CVDs). We investigated if a combination of natural activators of autophagy could modulate oxidative stress, platelet aggregation and endothelial cell survival and function in response to stress.
Ex vivo platelet aggregation and activation, H O production and autophagy were measured in platelets of subjects at high cardiovascular risk, including smokers, patients with metabolic syndrome (MetS) and patients with atrial fibrillation (AF). In vitro, the effects of a mixture of natural pro-autophagy molecules and antioxidants on platelets and human umbilical vein endothelial cells (HUVECs) were evaluated.
Autophagy appeared to be inhibited, whereas aggregation was increased in platelets from AF and MetS patients and in smokers, as compared with healthy subjects. Treatment of platelets isolated from these patients with a mixture composed of trehalose, spermidine, catechin and epicatechin (Mix1) or with a mixture composed of trehalose, spermidine and nicotinamide (Mix2), significantly reduced platelet activation and oxidative stress, and increased autophagy, compared with the effect of each compound alone. Similarly, treatment of HUVECs with a combination of these compounds exhibited beneficial effects and increased endothelial cell survival, nitric oxide bioavailability and angiogenesis in response to stress in a potentiated manner.
A combination of natural activators of autophagy could inhibit platelet activity and oxidative stress and improve endothelial cell survival and function in a potentiated manner representing a useful strategy to reduce the effect of risk factors on CVD occurrence.
This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc.
氧化应激和自噬活性不足与炎症过程有关，是许多心血管疾病（CVD）的共同特征。我们研究了自噬的天然激活剂组合是否可以调节氧化应激、血小板聚集以及内皮细胞在应激时的存活和功能。
在高心血管风险患者（包括吸烟者、代谢综合征（MetS）患者和心房颤动（AF）患者）的血小板中测量体外血小板聚集和激活、H 2 O 2 产生和自噬。在体外，评估天然促自噬分子和抗氧化剂混合物对血小板和人脐静脉内皮细胞（HUVEC）的影响。
与健康受试者相比，AF 和 MetS 患者以及吸烟者的血小板自噬似乎受到抑制，而聚集增加。与每种化合物单独处理相比，用由海藻糖、亚精胺、儿茶素和表儿茶素组成的混合物（Mix1）或由海藻糖、亚精胺和烟酰胺组成的混合物（Mix2）处理从这些患者分离的血小板可显著减少血小板激活和氧化应激，增加自噬。同样，用这些化合物的组合处理 HUVECs 可增强方式表现出有益的效果，增加内皮细胞存活、一氧化氮生物利用度和血管生成，以响应应激。
自噬的天然激活剂组合可以抑制血小板活性和氧化应激，并以增强的方式改善内皮细胞的存活和功能，这代表了一种减少危险因素对 CVD 发生影响的有用策略。
本文是关于细胞代谢和疾病的专题问题的一部分。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc.
