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Caffeic acid attenuates the inflammatory stress induced by glycated LDL in human endothelial cells by mechanisms involving inhibition of AGE‐receptor, oxidative, and endoplasmic reticulum stress
Author(s) -
Toma Laura,
Sanda Gabriela M.,
Niculescu Loredan S.,
Deleanu Mariana,
Stancu Camelia S.,
Sima Anca V.
Publication year - 2017
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.1373
Subject(s) - oxidative stress , apocynin , rage (emotion) , endoplasmic reticulum , glycation , chemistry , nadph oxidase , unfolded protein response , caffeic acid , inflammation , endothelial dysfunction , receptor , antioxidant , pharmacology , endocrinology , medicine , biochemistry , biology , neuroscience
Type 2 diabetes mellitus is a worldwide epidemic and its atherosclerotic complications determine the high morbidity and mortality of diabetic patients. Caffeic acid (CAF), a phenolic acid present in normal diets, is known for its antioxidant properties. The aim of this study was to investigate CAF's anti‐inflammatory properties and its mechanism of action, using cultured human endothelial cells (HEC) incubated with glycated low‐density lipoproteins (gLDL). Levels of the receptor for advanced glycation end‐products (RAGE), inflammatory stress markers (C reactive protein, CRP; vascular cell adhesion molecule‐1, VCAM‐1; monocyte chemoattractant protein‐1, MCP‐1), and oxidative stress and endoplasmic reticulum stress (ERS) markers were evaluated in gLDL‐exposed HEC, in the presence/absence of CAF. RAGE silencing or blocking, specific inhibitors for oxidative stress (apocynin, N ‐acetyl‐cysteine), and ERS (salubrinal) were used. The results showed that: (i) gLDL induced CRP synthesis and secretion through mechanisms involving NADPH oxidase‐dependent oxidative stress and ERS in HEC; (ii) gLDL–RAGE interaction, oxidative stress, and ERS stimulated the secretion of VCAM‐1 and MCP‐1 in HEC; and (iii) CAF reduced the secretion of CRP, VCAM‐1, and MCP‐1 in gLDL‐exposed HEC by inhibiting RAGE expression, oxidative stress, and ERS. In conclusion, CAF might be a promising alternative to ameliorate a wide spectrum of disorders due to its complex mechanisms of action resulting in anti‐inflammatory and antioxidative properties. © 2017 BioFactors, 43(5):685–697, 2017