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Review
. 2018 Nov:139:48-53.
doi: 10.1016/j.prostaglandins.2018.09.008. Epub 2018 Sep 29.

Mechanisms of isolevuglandin-protein adduct formation in inflammation and hypertension

Liang Xiao  1 , David M Patrick  1 , Luul A Aden  1 , Annet Kirabo  2
Affiliations
Review

Mechanisms of isolevuglandin-protein adduct formation in inflammation and hypertension

Liang Xiao et al. Prostaglandins Other Lipid Mediat. 2018 Nov.

Abstract

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.

Keywords: Hypertension; Inflammation; Isolevuglandins.

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Conflict of interest statement

The authors have declared that no conflict of interest exists.

Figures

Figure 1:
Figure 1:. IsoLG-protein adduct formation.
Isolevuglandins (IsoLGs) are formed from lipid peroxidation of arachidonic acid. They are highly labile and form covalent bonds with lysine residues of nearby proteins leading to formation of IsoLG-protein adducts.
Figure 2:
Figure 2:. Hypertensive stimuli leading to immune cell activation via IsoLG-protein adduct formation.
Hypertensive stimuli including angiotensin II, sympathetic outflow and excess dietary salt lead to increased NADPH oxidase-dependent production of reactive oxygen species (ROS) by antigen presenting myeloid derived cells. This leads to oxidation of arachidonic acid and formation of IsoLG-protein adducts. These are immunogenic and activate antigen presenting cells to produce inflammatory cytokines including IL 1b, IL6 and IL23. These myeloid cells activate T cell to proliferate and produce inflammatory cytokines including IL-17A, TNF-α and IFN-γ which lead to hypertension.
See this image and copyright information in PMC

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