Glycocalyx Degradation Induces a Proinflammatory Phenotype and Increased Leukocyte Adhesion in Cultured Endothelial Cells under Flow

• Published in: PloS one 2016-12, Vol.11 (12), p.e0167576-e0167576
• Main Authors: McDonald, Karli K, Cooper, Scott, Danielzak, Lisa, Leask, Richard L
• Format: Article
• Language: English
• Subjects: Adhesion; Aorta; Arteriosclerosis; Atherosclerosis; Biology and Life Sciences; Biomechanical Phenomena; Biomedical engineering; Cell Adhesion; Cell adhesion & migration; Cell culture; Cell Culture Techniques; Cell Line; Cell Line, Tumor; Chemical engineering; Chemokines; Coculture Techniques; Degradation; Destabilization; Development and progression; Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelium; Gene Expression Regulation; Genetic aspects; Genotype & phenotype; Glycocalyx - chemistry; Glycocalyx - metabolism; Humans; Hydrolysis; Inflammation; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Leukocytes; Leukocytes - metabolism; Leukocytes - pathology; Ligands; Mechanotransduction; Mechanotransduction, Cellular; Medicine and Health Sciences; Microscopy; Molecular modelling; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Pathogenesis; Phenotype; Physiological aspects; Physiology; Receptors; Research and Analysis Methods; Rheology; Shear stress; Shear stresses; Stress, Mechanical; Three dimensional models; White blood cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0167576

Leukocyte adhesion to the endothelium is an early step in the pathogenesis of atherosclerosis. Effective adhesion requires the binding of leukocytes to their cognate receptors on the surface of endothelial cells. The glycocalyx covers the surface of endothelial cells and is important in the mechanotransduction of shear stress. This study aimed to identify the molecular mechanisms underlying the role of the glycocalyx in leukocyte adhesion under flow. We performed experiments using 3-D cell culture models, exposing human abdominal aortic endothelial cells to steady laminar shear stress (10 dynes/cm2 for 24 hours). We found that with the enzymatic degradation of the glycocalyx, endothelial cells developed a proinflammatory phenotype when exposed to uniform steady shear stress leading to an increase in leukocyte adhesion. Our results show an up-regulation of ICAM-1 with degradation compared to non-degraded controls (3-fold increase, p