Xiao Liang, Patrick David M, Aden Luul A, Kirabo Annet
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, United States; Vanderbilt Institute for Infection, Immunology & Inflammation (VI4), Nashville, TN, United States.
Prostaglandins Other Lipid Mediat. 2018 Nov;139:48-53. doi: 10.1016/j.prostaglandins.2018.09.008. Epub 2018 Sep 29.
Inflammation has been implicated in the pathogenesis of hypertension and recent evidence suggests that isolevuglandin (IsoLG)-protein adducts play a role. Several hypertensive stimuli contribute to formation of IsoLG-protein adducts including excess dietary salt and catecholamines. The precise intracellular mechanisms by which these hypertensive stimuli lead to IsoLG-protein adduct formation are still not well understood; however, there is now evidence implicating NADPH-oxidase derived reactive oxygen species (ROS) in this process. ROS oxidize arachidonic acid leading to formation of IsoLGs, which non-covalently adduct to lysine residues and alter protein structure and function. Recent studies suggest that these altered proteins act as neo-antigens leading to an autoimmune state that results in hypertension. The goal of this mini-review is to highlight some of the hypertensive stimuli and the mechanisms contributing to IsoLG-protein adduct formation leading to inflammation and hypertension.
炎症与高血压的发病机制有关，最近的证据表明异前列烷（IsoLG）-蛋白质加合物发挥了作用。几种高血压刺激因素会导致IsoLG-蛋白质加合物的形成，包括过量的膳食盐和儿茶酚胺。这些高血压刺激因素导致IsoLG-蛋白质加合物形成的确切细胞内机制仍未完全了解；然而，现在有证据表明烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶衍生的活性氧（ROS）参与了这一过程。ROS氧化花生四烯酸导致IsoLG的形成，IsoLG与赖氨酸残基非共价结合并改变蛋白质的结构和功能。最近的研究表明，这些改变的蛋白质作为新抗原导致自身免疫状态，从而引发高血压。本综述的目的是强调一些高血压刺激因素以及导致IsoLG-蛋白质加合物形成从而引发炎症和高血压的机制。
