Biomedical Engineering Reference
In-Depth Information
receptor, preventing the removal of excess LDL cholesterol [
54
]. In both cases,
health complications arise from significant accumulation of cholesterol in the
bloodstream.
One effect is pathological changes to vascular structure and function. Hyper-
cholesterolemia has been reported to induce oxidative stress on the endothelial
cells, leading to vascular wall damage [
55
]. In turn, endothelial dysregulation due
to hypercholesterolemia has been shown to promote vascular remodeling [
56
,
57
].
Another major complication of hypercholesterolemia is widespread microvas-
cular inflammation that occurs long before lethal vascular remodeling (e.g., ath-
erosclerosis) and that ultimately drives downstream vasculopathy [
58
,
59
].
Leukocytes are recruited in large numbers, endothelial cells secrete additional
cytokines, and adhesion molecules are upregulated, all of which contribute to an
inflammatory phenotype [
60
]. Researchers have observed that, under the chronic
inflammatory conditions imposed by hypercholesterolemia, activated leukocytes
are capable of obstructing blood flow through capillary networks [
61
]. The impaired
flow through the capillaries results in increased vascular resistance, another
downstream effect of hypercholesterolemia on the microcirculation. Notably, neu-
trophils have been implicated in microvascular dysfunction due to hypercholes-
terolemia [
59
,
62
], a feature that also characterizes morbid obesity [
63
].
3 Neutrophils and Their Rheological Influence
on the Microcirculation
The downstream complications of obesity, hypertension, and hypercholesterolemia
indicate that chronic inflammation is a shared trait. Consequently, it is likely that
many of the cells activated during chronic inflammation contribute to vascular
dysfunction associated with these pathological states. One such cell, the neutro-
phil, may play an early role in disease progression. For example, it has been
observed in women that obesity is associated with elevated neutrophil adhesion in
the vasculature [
46
]. Elevated neutrophil adhesion/activity is also related to
hypercholesterolemia and downstream cardiovascular diseases such as athero-
sclerosis [
64
]. The fact that neutrophils have been shown to play a role in the
development of chronic inflammation during hypertension and hypercholesterol-
emia points to their role in obesity-related pathogenesis/pathobiology. Moreover,
the role they play likely involves their activation state.
3.1 The Neutrophils and Their Activation State
Leukocytes account for *1 % of the blood cell volume. The polymorphonucle-
ated granulocytes, largely dominated by the neutrophils, are among the most
numerous of the leukocytes. The dominant presence of the neutrophils in the blood
Search WWH ::
Custom Search