**1. Introduction**

222 Lipoproteins – Role in Health and Diseases

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This chapter focuses on the potential contributions of the blood-borne neutrophils to hypercholesterolemia-related pathophysiology (e.g., thrombus formation, embolism, heart attack, stroke, etc.). Neutrophils are immersed in the cholesterol-abundant plasma of blood and play critical roles in the acute inflammatory response of the body to infection or tissue damage. Because of their high degree of sensitivity to inflammatory agonists and their arsenal of potent microbicidal and tissue degradative agents, a number of redundant cellular mechanisms exist to control or "turn-off" the inflammatory processes by these cells under physiological (non-pathological) conditions. Failure of these mechanisms leads to sustained levels of cell activity that contribute to a chronic inflammatory phenotype with the continuous release of proteases and cytokines as well as the potential to elicit non-specific damage to host tissues. Alternatively, chronic neutrophil activity may impair tissue perfusion via its effects on the rheological flow behavior of blood particularly in terms of the ability of leukocytes to transit the microcirculation[1]. Such potential damage mechanisms are thought to govern an increasing number of human pathological scenarios (e.g., Alzheimer's, diabetes, vascular disease) that correlate with a chronic inflammatory state. In this regard, chronic inflammation has gained recognition in the scientific community and even in the mainstream national media (e.g., Time[2] and Newsweek[3] magazines) as a common denominator for human diseases. The question is whether the dysregulation of neutrophil activity is a significant component of this potential disease mechanism.

We address this issue from a mechanobiological perspective by presenting evidence that supports a role of impaired neutrophil mechanotransduction of hemodynamics-derived fluid flow in the pathogenesis of hypercholesterolemia-linked diseases. For this purpose, we

© 2012 Zhang and Shin, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

will first discuss the link between chronic inflammation and hypercholesterolemia and then highlight the neutrophil involvement in the pathophysiology of related cardiovascular diseases, e.g. atherosclerosis and microvascular dysfunction. To further exemplify this link, we will explain the potential mechanism(s) by which cholesterol in blood may impact the biochemical regulation of neutrophil activity at the cellular level. Finally, we will introduce our own evidence as well as those of others pointing to dysregulated neutrophil mechanotransduction as an important component of hypercholesterolemic pathologies.
