Rheology

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Patients with hypertension have increased common carotid artery IMT and lower mean shear stress with a negative correlation between shear stress and IMT in hypertensives. In the general population, decreased shear stress may contribute to atherosclerosis (16). It was suggested that the ubiquitous atherosclerotic changes in fetal and pediatric subjects when serum cholesterol levels are normal demonstrate the importance of repetitive hemodynamic stresses, rather than hypercholesterolemia, in atherosclerosis (reviewed in ref. 17).

Local blood flow conditions modulate the production of vasoactive substances, NO and endothelin (ET)-l, by human umbilical vein endothelial cells (HUVEC) (18) and shear stress upregulates monocyte chemo-tactic factor (MCP)-l, interleukin (IL)-8, ET-1, and connective tissue growth factor (CTGF) (19) and induces collagen XII expression, which may stabilize the vascular structure in HUVEC (20).

Laminar flow exposure leads to activation of antioxidant genes in endothelial cell (EC) (21 jand promotes EC survival and quiescence and the secretion of substances that promote vasodilation and anticoagulation (22). Flow induces an increase in oxidative stress in EC, which is dependent on the pulsatile nature of flow (23).

In rabbits, exposure of the arterial wall to low wall shear stress may activate ECs increasing intercellular permeability, which in turn increases the vulnerability of these regions to atherosclerosis (24).

Table 1

Some Factors Associated With Development of Atherosclerosis

LDL-cholersterol* Total cholesterol* Total cholesterol/HDL* Smoking*

Increased triglycerides

Hypertension

Obesity

Diabetes

Left ventricular hypertrophy Hyperinsulinemia Increased fibrinogen Herpes infection Lp(a)

Homocysteine

Chlamydia pneumoniae

Hypothyroidism

PAF-AH

Phospholipase all Low wall shear stress

♦Indicates the strongest correlation with atherosclerosis development.

Also, the role of L-selectin in various situations of leukocytes recruitment could be affected, among other reasons, by wall shear (25). L- selectin is a leukocyte adhesion molecule that is rapidly shed after leukocyte activation so that it appears to be decreased in CAD (26).

Pulsatile oscillatory shear stress induces a procoagulant phenotype of human EC by increasing tissue factor mRNA and protein expression and activity (27).

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