Biomedical Engineering Reference
In-Depth Information
activation and nitric oxide (NO) production.
Also, in patients with diabetes mellitus,
development of endothelial dysfunction can be associated with hyperglycemia,
insulin resistance, and oxidative stress.
In this regard, acute hyperglycemia in
normal subjects was observed to induce an increase in plasma sICAM-1 but not
plasma sVCAM-1 concentrations.
L-arginine supplementation in hyperglycemic
diabetic patients was found to normalize elevated sICAM-1 plasma levels. h ese
results suggest that NO might have an inhibitory ef ect on the expression of some
cellular AMs in human vascular endothelial cells (Marfella
et al.
2000).
h e following explains a possible basis of the close association between
sICAM-1 and SVD in patients with diabetes mellitus. h e activation of vascular
endothelium by elevated blood glucose levels induces ICAM-1 expression and
then ICAM-1 facilitates adhesion of leukocyte, especially neutrophils to the
vascular endothelium, which causes small vessels in the brain to occlude, and
leads to development of SVD such as silent brain infarction (SBI). In patients with
diabetes mellitus, endothelial dysfunction can be worsened when oxidative stress
enhances the blood-brain barrier (BBB) permeability, which may promote the
development of microangiopathy such as SBI and WMLs.
Oxidative stress increases
tight junction permeability in vascular endothelium, leading to disruption of the
BBB.
Starr
et al.
(2003) reported that increased BBB permeability was detected in
patients with type 2 diabetes on MRI. A
recent study investigating an association
between SBI incidence and AMs showed that high concentrations of sICAM-1
are signii cantly associated with SBI incidence and the relationship between
endothelial dysfunction and presence of SBI may be stronger in diabetic patients
that there is a greater possibility of endothelial dysfunction developing in diabetic
patients with SVD than in non-diabetic subjects.
h e presence of vascular risk factors such as hypertension, diabetes and smoking
increases the production of reactive oxygen species in mitochondria, which can
cause cell membrane damage and induce apoptosis. On the other hand, these risk
factors decrease the production of NO, which is important to maintaining cerebral
blood l ow. h is situation facilitates the progression of endothelial dysfunction.
Previous study demonstrated that eNOS activity is reduced and NO production
disrupted in SVD, and the results of more recent research have indicated the
possibility that BBB dysfunction is an important mechanism in brain disorders
due to cerebral small-vessel and microvessel disease (Wardlaw
et al.
2008). h ese
i ndings suggest that the systemic progression of endothelial dysfunction is an
important reason for the pathogenesis in SVD.
In a study on 47 patients with isolated lacunar infarction, 63 patients with
ischemic leukoaraiosis, and 50 controls, Hassan
et al.
(2003) graded the size of
lacunar infarctions and severity of leukoaraiosis on CT or MRI to determine
whether there were dif erences in markers of endothelial activation and damage
between patient groups. h ese results showed that the mean levels of ICAM-1
