Premium
Effect of Hypertension on Dendritic Cells and a potential role of Isoketals
Author(s) -
Kirabo Annet,
Chen Wei,
Wu Jing,
Thabet Salim,
Bikineyeva Alfiya,
Dikalov Sergey,
Roberts Jackson,
Amarnath Venkataraman,
Davies Sean S,
Harrison David Glenn
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.872.16
Subject(s) - angiotensin ii , oxidative stress , reactive oxygen species , superoxide , chemistry , renin–angiotensin system , medicine , pathophysiology of hypertension , endocrinology , blood pressure , biochemistry , enzyme
We have previously shown that angiotensin II‐infusion activates dendritic cells (DCs) and that this contributes to blood pressure elevation. Reactive oxygen species (ROS) also contribute to hypertension, but the interaction of hypertensive stimuli, oxidative stress and DC activation are not defined. Isoketals are highly reactive oxidation products of arachidonic acid that cross‐link lysine residues on proteins. These can alter protein function and become antigenic. We sought to determine if hypertension alters DC ROS production and if isoketal formation is involved in hypertension. We found that angiotensin II infusion increased DC superoxide production by >50%. Angiotensin II also caused a massive accumulation of isoketals in various tissues including the heart, kidney and vasculature. In additional experiments, we co‐administered salicylamine, a potent scavenger of isoketals. Salicylamine attenuated development of angiotensin II‐induced hypertension (142.59 ± 8.98 mmHg versus 175.53 ± 5.19 mmHg in control mice). These studies show that hypertension causes oxidative stress in DCs. Moreover, isoketal modified proteins may serve as neoantigens that trigger hypertension.