Trial Information

Investigation of the Influence of Gender on Cardiovascular Function and Inflammation

We now know that one of the earliest events involved in precipitating disease of the heart
and blood vessels is the phenomenon of inflammation and that this inflammation is a key
process involved in dampening the protective nature of the inner lining (the endothelium) of
the blood vessel wall, called endothelial dysfunction. In healthy arteries the endothelium
releases a number of factors that maintain the health of the blood vessel. These factors act
to keep the blood vessel in an open and dilated state and prevent the furring up of the
vessel by actively inhibiting the cell components of the blood from collecting at the
endothelium and blocking the flow of blood through the artery. Recent research in animals
has demonstrated that one of the key components of inflammation i.e. the attraction of white
cells, is reduced in females compared to males and that this is due to a reduced expression
of key proteins called 'adhesion molecules', an in particular a molecule called P-selectin,
on the endothelium. We now wish to determine whether similar differences in white cell
attraction and adhesion molecules exist between the sexes in humans and whether these
differences might underlie differences in endothelial function.

To investigate this possibility we will use a validated model of acute inflammation in
healthy volunteers. To determine whether susceptibility to inflammation-induced endothelial
dysfunction is distinct between the sexes we will use typhoid vaccine to induce mild
inflammation throughout the body including the blood vessels. Previous published studies
have shown that vaccination induces an acute inflammation that results in a temporary
(reversed within 48h) dysfunction of the endothelium that can be measured using a range of
non-invasive techniques called ultrasound flow-mediated dilatation and pulse wave velocity.
We will use these techniques together with biochemical measurements to determine possible
associations of endothelial dysfunction with specific inflammatory factors. In particular
we will investigate the possibility that differences in the expression of the adhesion
molecule P-selectin might have a role to play in differences between the sexes.