Impaired Neutrophil Mechanoregulation by Fluid Flow: A Potential Contributing Factor for Microvascular Dysfunction in Obesity - The Mechanobiology of Obesity and Related Diseases - page 198

2.2 Obesity and Hypertension
Obesity-related vascular pathobiology plays a role in the development and pro-
gression of hypertension [ 36 ]. Reportedly, 65-75 % of hypertensive individuals
exhibit excessive weight gain [ 37 , 38 ]. These statistics point to a link between
obesity-related vascular dysfunction and hypertension. Furthermore, obesity and
hypertension are associated with an inflamed blood state, including enhanced
levels of CRP and other pro-inflammatory cytokines [ 39 , 40 ].
Notably, such a chronic inflammatory state may lead to downstream effects
including microvascular dysfunction. For example, hypertension has been shown
to raise peripheral hemodynamic resistance even after brief periods of therapeutic
treatment [ 41 ]. Interestingly, obesity and hypertension are both associated with
endothelial dysregulation as it relates to the control of vasomotor activity in
arterioles [ 42 - 44 ]. Conceivably, the enhanced release of inflammatory cytokines
due to morbid obesity or hypertension may contribute to microvascular dysfunc-
tion by stimulating leukocyte-mediated damage to the endothelium responsible for
regulating blood vessel vasomotor activity [ 13 ].
Additionally, both hypertension and obesity are associated with enhanced
endothelial expression of cell adhesion molecules as well as elevated leukocyte
counts and activation [ 45 ]. Notably, neutrophils have been recognized as early
players in this regard [ 46 ]. This manifestation of obesity and hypertension may
further contribute to pathological elevations in microvascular flow resistance by
promoting leukocyte adhesion in the microcirculation [ 47 ].
2.3 Obesity and Hypercholesterolemia
Obesity and hypercholesterolemia share many commonalities including patho-
logical release of pro-inflammatory cytokines and CRP [ 48 ]. Evidence indicates a
link between hypercholesterolemia and obesity [ 6 ], however there is debate as to
which develops first. One study, the Bogalusa Heart Study, provides evidence of
the contribution of hypercholesterolemia to obesity [ 49 ]. However, other published
findings indicate that obesity appears to precede the abnormal increase in cho-
lesterol content [ 50 , 51 ]. Nevertheless, it is clear that a link exists between the two,
as downstream effects such as chronic inflammation and vascular dysfunction are
common traits of both conditions.
Like obesity, hypercholesterolemia is a strong risk factor for cardiovascular
diseases (e.g., heart attack, stroke) associated with high mortality/morbidity [ 52 ].
The cause of hypercholesterolemia may be dietary or genetically linked, but both
involve significant increases in blood levels of low-density lipoprotein (LDL).
Consumption of a high-fat diet may generate large amounts of LDL, raising the
blood cholesterol levels above normal [ 53 ]. Alternatively, blood cholesterol
levels may increase due to genetic mutations that cripple the activity of the LDL