Premium
Chlorinated Lipids Induce Increased Cortical Stiffness in Microvascular Endothelial Cells
Author(s) -
Birkhead Travis Michael,
Kalogeris Theodore,
Yu Hong,
Meininger Gerald,
Ford David,
Ronald Korthuis
Publication year - 2016
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.30.1_supplement.lb782
Subject(s) - chemistry , hypochlorous acid , endothelium , myeloperoxidase , inflammation , endothelial dysfunction , microbiology and biotechnology , endothelial stem cell , vascular permeability , biophysics , biochemistry , endocrinology , immunology , in vitro , biology
Elastic properties of the vascular endothelium are critical to its role in controlling blood flow, pressure, vascular tone, adhesion of platelets and leukocytes, permeability and other homeostatic functions. Dysregulation of these endothelial functions are hallmarks of the inflammation produced in response to ischemia‐reperfusion, but it is not clear to what extent altered endothelial elasticity plays a role in the endothelial response to specific pro‐inflammatory stimuli. Cellular and plasma lipids that have been chlorinated by reacting with hypochlorous acid (HOCl) produced by neutrophil myeloperoxidase (MPO) have been shown to increase several markers of endothelial inflammatory activation. However, their effect on endothelial elasticity is unknown. We have begun to explore this issue in cultured endothelial cells. Human microvascular endothelial cells (HMEC‐1) were cultured to varying levels of confluence, incubated with 10 μM of 2‐chlorohexadecanoic acid (Cl‐HA), hexadecanoic acid (HA), 2‐chlorohexadecanal (Cl‐HDA), or hexadecanal (HDA), or 10 ng/ml TNF‐α, and cortical stiffness was measured using atomic force microscopy (AFM). Treatment with chlorinated lipids showed confluence‐dependent increases in stiffness, while non‐chlorinated lipids tended to decrease stiffness when compared with EtOH diluent. While the effect of chlorinated lipid varied with confluence, TNF‐α (positive control) produced consistent results independent of culture confluence. These results show for the first time, that the chlorinated lipids known to be produced through reaction with neutrophil MPO‐derived HOCl, increase cortical stiffness in microvascular endothelial cells. Support or Funding Information RO1‐GM115553 & R01‐AA221081