Apostolova Nadezda, Rocha Milagros, Rovira-Llopis Susana, Banuls Celia, Falcon Rosa, Castello Raquel, Hernandez-Mijares Antonio, Victor Victor M
FISABIO-University Hospital Doctor Peset, Avda Gaspar Aguilar 90, 46017, Valencia, Spain.
Curr Med Chem. 2014;21(25):2989-3006. doi: 10.2174/0929867321666140601200416.
Endothelial dysfunction involving dysfunctional mitochondria precedes the development of cardiovascular diseases. This impairment results from an increase in reactive oxygen species, which leads to oxidative stress and a reduced bioavailability of nitric oxide. It has been demonstrated that oxidative stress and alterations in glucose and lipid homeostasis (e.g. hyperinsulinemia, hyperglycemia, insulin resistance and dyslipidemia) are linked to mitochondrial impairment and that all of them contribute to endothelial dysfunction. Anti-hyperlipidemic drugs such as statins, anti-hypertensive drugs and angiotensin receptor antagonists have been shown to exert protection through anti-oxidative stress mechanisms. Other substances with antioxidant properties, such as vitamins, are also capable of abolishing the oxidative stress associated with cardiometabolic diseases. However, the results obtained with general antioxidants in clinical trials are contradictory, perhaps due to the unspecific nature of the targets selected. This study correlates endothelial dysfunction and mitochondrial dysfunction and examines current research for the selective targeting of specific molecules (such as ·NO donors and antioxidants) to mitochondria with the aim of protecting the endothelium against oxidative stress in cardiovascular diseases.
涉及功能失调线粒体的内皮功能障碍先于心血管疾病的发生。这种损伤是由活性氧增加导致的，活性氧增加会引发氧化应激并降低一氧化氮的生物利用度。已经证明，氧化应激以及葡萄糖和脂质稳态的改变（如高胰岛素血症、高血糖、胰岛素抵抗和血脂异常）与线粒体损伤有关，并且所有这些因素都导致内皮功能障碍。他汀类等抗高血脂药物、抗高血压药物和血管紧张素受体拮抗剂已被证明可通过抗氧化应激机制发挥保护作用。其他具有抗氧化特性的物质，如维生素，也能够消除与心脏代谢疾病相关的氧化应激。然而，在临床试验中使用一般抗氧化剂获得的结果相互矛盾，这可能是由于所选靶点的非特异性。本研究将内皮功能障碍与线粒体功能障碍相关联，并研究当前针对特定分子（如一氧化氮供体和抗氧化剂）选择性靶向线粒体的研究，目的是保护内皮免受心血管疾病中的氧化应激。
