Biomedical Engineering Reference
In-Depth Information
In 2010 these statistics translated into approximately $150 billion in annual
medical costs since obese individuals are more likely to develop disease, partic-
ularly those related to the cardiovascular system [ 4 , 5 ]. While obesity itself may
not necessarily be a direct cause of cardiovascular diseases, it places an unhealthy
burden on the body that contributes to downstream pathophysiology, including
pathological elevations in blood pressure (i.e., hypertension) and blood cholesterol
(i.e., hypercholesterolemia) [ 6 ]. Notably, these two pathological conditions are
associated with a chronic inflammatory blood state typified by a change in the
physiological regulation of the blood-borne leukocytes including their sustained
activation in the circulation [ 7 - 9 ].
Neutrophils, the dominant leukocytes in blood, are the first responders of the
acute inflammatory response. Because of their high sensitivity to noxious stimuli
and their enormous destructive potential, neutrophil inactivity does not solely
result from an absence of inflammatory agonists. Neutrophils are, in fact, tightly
regulated to ensure their inactivity under physiological (i.e., non-inflamed, non-
pathogenic) conditions. A failure to do so has been linked to sustained neutrophil
activity in the blood that may ultimately drive downstream tissue injury [ 10 ].
Specifically, while dysregulated neutrophil activation may result in continuous
release of proteases and cytokines that elicits non-specific damage to host tissues,
it may also impair tissue perfusion via its effects on blood rheology and leukocyte
passage through the microcirculation [ 7 ]. Such potential damage mechanisms are
thought to govern a number of human pathologies (e.g., vascular disease) asso-
ciated with chronic inflammation.
A growing body of evidence [ 11 ] indicates that mechanotransduction of
hemodynamic shear stress appears to be one important control mechanism that
restricts the biological activity of neutrophils under physiological (i.e., non-
inflamed, non-pathogenic) conditions. Upon its impairment, elevated levels of
activated neutrophils in blood are expected to ensue with an impact on micro-
vascular perfusion that may eventually cause tissue damage. Interestingly, there is
evidence suggesting that impaired neutrophil shear responsiveness is a feature of
both hypertension and hypercholesterolemia [ 8 , 9 , 12 ]. Considering obesity is
strongly linked to hypertension and hypercholesterolemia upstream of lethal
vascular trauma (e.g., heart attack, stroke), it may also be connected to impaired
neutrophil mechanobiology. The potential connection between neutrophil
mechanosensitivity and obesity is explored as the central focus of this chapter.
2 Chronic Neutrophil Activity and the Microcirculation
in Obesity
The ever-increasing prevalence of obesity is placing more individuals at risk to
develop cardiovascular-related diseases. Obesity is a known risk factor for several
diseases such as diabetes, hypertension, or hypercholesterolemia [ 13 ]. In recent
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