Lp-PLA2 and Coronary Atherosclerosis in Humans

The majority of the acute coronary events are caused by coronary artery segments with
minimal luminal disease, but with potentially significant vascular wall inflammation and
oxidative stress leading to plaque vulnerability. It has become apparent that an initial
injury at the endothelial surface, is the primary site of the mechanisms involved and a role
for vascular inflammation and the interaction with oxidative stress continues to emerge.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel biomarker for vascular wall
inflammation that circulates in the blood bound to both low density (LDL) and high density
(HDL) lipoprotein and promotes vascular inflammation. Circulating levels of Lp-PLA2 mass and
activity are an independent risk factor for cardiovascular events. Recent studies,
demonstrating that Lp-PLA2 is also associated with coronary endothelial dysfunction.
However, the relationship between Lp-PLA2 and early atherosclerotic changes in the coronary
arteries, and the contribution of lipoprotein binding to the deleterious potential of Lp-
PLA2 have not been elucidated. Our working hypothesis is that the endogenous local
activation of the Lp-PLA2 pathway plays an integral role in early coronary atherosclerosis
and contributes to the mechanism of coronary endothelial dysfunction and the structural and
mechanical properties reflecting plaque vulnerability. Thus, the current application will
characterize prospectively the correlation between the functional, mechanical, and
structural vascular wall properties, and the systemic as well as the coronary activity of
the Lp-PLA2 pathway.