Nasoni M G, Crinelli R, Iuliano L, Luchetti F
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, Latina, Italy.
Free Radic Biol Med. 2023 Nov 1;208:178-185. doi: 10.1016/j.freeradbiomed.2023.08.008. Epub 2023 Aug 5.
Oxidized LDL (oxLDL) and oxysterols are known to play a crucial role in endothelial dysfunction (ED) by inducing endoplasmic reticulum stress (ERS), inflammation, and apoptosis. However, the precise molecular mechanisms underlying these pathophysiological processes remain incompletely understood. Emerging evidence strongly implicates excessive nitric oxide (NO) production in the progression of various pathological conditions. The accumulation of reactive nitrogen species (RNS) leading to nitrosative stress (NSS) and aberrant protein S-nitrosylation contribute to NO toxicity. Studies have highlighted the involvement of NSS and S-nitrosylation in perturbing ER signaling through the modification of ER sensors and resident isomerases in neurons. This review focuses on the existing evidence that strongly associates NO with ERS and the possible implications in the context of ED induced by oxLDL and oxysterols. The potential effects of perturbed NO synthesis on signaling effectors linking NSS with ERS in endothelial cells are discussed to provide a conceptual framework for further investigations and the development of novel therapeutic strategies targeting ED.
氧化型低密度脂蛋白（oxLDL）和氧化甾醇通过诱导内质网应激（ERS）、炎症和细胞凋亡，在内皮功能障碍（ED）中发挥关键作用。然而，这些病理生理过程背后的确切分子机制仍未完全清楚。新出现的证据强烈表明，在各种病理状况的进展中，过量一氧化氮（NO）的产生起了重要作用。活性氮物质（RNS）的积累导致亚硝化应激（NSS）和异常的蛋白质S-亚硝基化，这会造成NO毒性。研究强调了NSS和S-亚硝基化通过修饰神经元中的内质网传感器和驻留异构酶，参与扰乱内质网信号传导。本综述聚焦于现有证据，这些证据有力地将NO与ERS联系起来，并探讨了在oxLDL和氧化甾醇诱导的ED背景下的可能影响。讨论了内皮细胞中NO合成紊乱对连接NSS与ERS的信号效应器的潜在影响，为进一步研究和开发针对ED的新型治疗策略提供概念框架。
