Impaired Neutrophil Mechanoregulation by Fluid Flow: A Potential Contributing Factor for Microvascular Dysfunction in Obesity - The Mechanobiology of Obesity and Related Diseases - page 215

6 Concluding Remarks
To date, the accumulated evidence points to shear stress mechanotransduction as
an important negative control mechanism for neutrophils flowing in the blood
under non-inflamed conditions and, thus, an important mediator of circulatory
homeostasis. For the most part, the pathobiology of obesity is a process that takes
decades to develop into a serious, life-threatening disease state that occurs in
parallel with the development of chronic inflammation involving neutrophil acti-
vation in the blood.
Based on the evidence presented in this chapter, it is possible that the patho-
biology of obesity may result, at least in part, from a putative disruption of the cell-
deactivating effects of fluid shear stress mechanotransduction on the neutrophils.
The possibility that obesity precedes a loss of neutrophil sensitivity to fluid flow
stimuli and leads to pathological situations implicates a wide range of cardio-
vascular (and non-cardiovascular) diseases associated with hypertension and
hypercholesterolemia, including diabetes [ 150 , 151 ]. However, this hypothesis
remains to be directly tested. The critical issues are to increase efforts to define the
link between obesity, chronic inflammation, and impaired neutrophil mechano-
transduction, as well as to determine if chronic inflammation precedes or results
from impairment of neutrophil mechanoregulation. Further experimental analyses
are therefore needed to link the cell surface properties, the flow sensors, the
extracellular flow environment, and the influence of obesity on these factors. In
turn, the insight derived from these studies may then be related back to micro-
vascular physiology and pathobiology. The hope is that by fully defining the role
of hemodynamic stress in the regulation of leukocytes, particularly the neutrophils,
one may gain a better understanding of their role in the pathogenesis of cardio-
vascular diseases related to obesity.
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