Impaired Neutrophil Mechanoregulation by Fluid Flow: A Potential Contributing Factor for Microvascular Dysfunction in Obesity

In this chapter, we discuss evidence that potentially implicates impaired neutrophil responses to shear stress as a putative factor in obesity-related cardiovascular disease. We do so by presenting evidence connecting obesity with microvascular disorders due to chronic inflammation and highlighting this link in the setting of hypertension and hypercholesterolemia. Furthermore, the potential impact of neutrophils on these obesity-related disease processes is discussed. Notably, both hypertension and hypercholesterolemia are associated with a deficiency in the neutrophil responsiveness to fluid shear stress. In this regard, we define the neutrophil responses to shear stress exposure and how these responses may play a role in microvascular function under physiological conditions as well as how their impairment may result in microcirculatory dysfunction. Finally, we point to data consistent with an impaired neutrophil shear sensitivity being a manifestation of obesity, particularly as it relates to hypertension and hypercholesterolemia. In this regard, we aim to suggest a novel perspective; specifically, that impaired neutrophil shear sensitivity precedes a chronic inflammatory state and serves as a putative source of obesity-related pathobiology.