Studies investigating sex hormone influences on heart disease
Young men are twice as likely as young women to die from
cardiovascular disease. This could be due to genetic, lifestyle and/or
hormonal influences. Hormones are readily amenable to therapeutic
intervention and a lot of research has focussed on elucidating the
influence of female hormones, estrogens, on cardiovascular disease.
However, in our laboratory we are instead focussing on the effects of
male hormones, androgens, on atherosclerosis. The hypothesis is that
life long exposure to androgens may predispose young men to earlier
atherosclerotic plaque development. If androgens underlie, even partly,
the gender difference in cardiovascular disease, then careful
consideration must be given to the increasing clinical application of
androgens in the treatment of hormone deficiency states and for hormonal
Our ongoing research has identified a novel androgen-sensitive step
in the earliest stage of atherosclerotic plaque development, namely the
increased expression of the key adhesion molecule, vascular cell
adhesion molecule-1 (VCAM-1). VCAM-1 mediates the binding, and
subsequent migration, of monocytes into the vessel wall. The androgen
stimulated increase in VCAM-1 expression is dependent on the activation
of the key inflammatory regulator, nuclear factor-kappaB. These findings
may provide clues to the earlier onset of atherosclerosis in men.
Further studies are now underway to more fully explore the molecular
pathways triggered by androgens in all key vascular cells associated
with atherosclerosis including monocytes, endothelial cells and smooth
We are also using genetic mouse models of cardiovascular disease to
study why men are predisposed to earlier onset cardiovascular disease.
One of our major studies is based on the Barker hypothesis that prenatal
exposure to nutritional and hormonal effects can impact on late-life
degenerative diseases, including cardiovascular disease. In this study
we are determining the effect of pre-natal- and peri-natal androgen
exposure on late-life cardiovascular disease.
© 2010 Heart Research Institute Ltd ABN 41 003 209 952