Regulation of Endothelial Activation and Vascular Inflammation by Shear Stress - Bioanalysis Advanced Materials Methods and Devices - page 77

Abbreviations

MKP-1 Mitogen activated protein kinase phosphatase 1

KLF2 Kruppel like factor 2

Nrf2 Nuclear factor erythroid 2-related factor 2

VCAM-1 Vascular cell adhesion molecule-1

PECAM-1 Platelet-endothelial cell adhesion molecule-1

ICAM-1 Intracellular cell adhesion molecule-1

MCP-1 Monocyte chemoattractant protein 1

JNK c-Jun N-terminal kinase

ATF2 Activating transcription factor 2

NF- k B Nuclear factor k -light-chain-enhancer of activated B cells

NOS Nitric oxide

6.1 Introduction

Inflammation of vascular tissues is induced in response to harmful stimuli such as
chemicals, pathogens or injury. Vascular inflammation involves the recruitment of
leukocytes, also known as white blood cells (monocytes, macrophages, dendritic
cells, neutrophils, and lymphocytes) to the site of injury. The vascular system is
lined with a monolayer of endothelial cells termed as the endothelium. This
monolayer of cells performs various functions such as acting as a mechanical
barrier and an anticoagulant, maintaining an anti-inflammatory environment,
facilitating physiological control of vasoregulation, and modulating vascular per-
meability. Endothelial infiltration by circulating leukocytes is comprised of a
multistep process that involves rolling of the leukocytes on the endothelium,
attachment of the leukocytes to the endothelium, and transmigration of the
leukocytes across the endothelial cells lining the blood vessel walls [ 1 ]. These
processes are mediated by several different receptors called selectins, addressins,
and integrins on the leukocytes and their subsequent interaction with adhesion
molecules expressed on the surface of the endothelial cells. The adhesion molecules
on endothelial cells include E-selectin, intracellular cell adhesion molecule-1
ICAM-1 (CD54), and vascular cell adhesion molecule-1 VCAM-1 [ 2 , 4 ].
The location of endothelial cells within the vascular endothelium is such that
they are constantly exposed to mechanical forces such as pressure, circumferential
stretch or tension and shear stress. Shear stress is a biomechanical quantity that is
determined by factors such as blood flow velocity, vessel geometry and local
fluid viscosity. Shear stress may be computationally estimated using fluid dynamics
models. The numerical calculation of wall shear stress has been the topic of
numerous studies, both in relation to larger scale flow features such as flow
detachment and recirculation zones (e.g., [ 26 ]) as well as on significantly smaller
scales (e.g., [ 24 ]). Particularly the study of the role of nitric oxide and the develop-
ment of atherosclerotic plaque has been well studied in the past (e.g., [ 23 ]).