Biomedical Engineering Reference
In-Depth Information
and those with MetS. Ethnic dif erences in circulating adhesion molecules and
the relationship with MetS have been reported and need further investigation.
Expression of cellular adhesion molecules is increased by activation of the nuclear
factor-kappaB (NF-κB) pathway and this may provide a therapeutic target for
disease prevention. Activation of cellular adhesion molecules may also play a role
in the observed association between sleep and cardiovascular disease.
INTRODUCTION
Ischemic heart disease and cardiovascular disease (CVD) remain the most common
causes of death. While 'traditional' risk factors such as blood pressure and serum
lipids may account for a large proportion of an individual's risk, these factors do
not explain it entirely. Evidence increasingly suggests that inl ammatory pathways
may provide the common underlying mechanism for the development of these
diseases. Adhesion molecules have been implicated in early atherosclerotic lesion
development (Krieglstein and Granger 2001) and plasma levels of intracellular
adhesion molecule 1 (ICAM-1) and E-selectin may act as markers of atherosclerosis
and the development of coronary heart disease (CHD) (Hwang
et al.
1997). Ethnic
dif erences exist, however, in these inl ammatory mediators and the prevalence of
CVD and CHD (Miller
et al.
2003, Miller and Cappuccio 2007a).
Innate Immune System and TLRs
h e innate immune system is the system conserved by evolution that allows the
body to respond immediately to perceived threats to bodily integrity. It is related
to, but completely distinct from, the acquired immune system. Generalized
dysfunction of the endothelial cells (which cover the walls of the arteries and veins)
may precede the development of atherosclerosis and underlie the development of
both CVD and CHD. h is process is initiated by the accumulation of macrophages
and low-density lipoproteins (LDL), which lead to an activation of innate immune
toll-like receptors (TLRs). h ese combine with the pattern recognition molecule
CD14 to form a complex (TLR4-CD14), which activates the nuclear factor-
kappaB (NF-κB) pathway. Activation of this pathway mediates adhesion molecule
expression, cytokine production and associated local inl ammation (Miller and
Cappuccio 2007a). Leukocyte adhesion molecules and chemokines promote
recruitment of monocytes and T cells. Monocytes dif erentiate into macrophages
and further upregulate pattern recognition receptors that internalize accumulated
lipoproteins in the intima to form foam-cells and subsequently atherosclerotic
plaques. T cells in lesions recognize local antigens and mount T helper-1
responses with secretion of pro-inl ammatory cytokines that contribute to local
inl ammation and plaque growth. Prolonged inl ammatory activation may lead to
local proteolysis, plaque rupture and thrombus formation, which causes ischemia,
