Aortic valve disease (AVD) is a common cardiac condition which afflicts ~25% of individuals over 65. It is associated with a 50% increased risk of mortality and incidence rates differ substantially between the two sexes. There are no pharmacological treatments, and risky surgical replacement of the valve is required when it becomes fibrotic, calcified, and impedes proper pumping of the heart.
Little is known about how AVD develops, and so the purpose of my research is to better understand this process. I have focused on a small peptide whose expression in the aortic valve is three times higher in males than females. Using mice genetically deficient in this protein, my work has determined that it plays a key role in protecting against AVD onset. I also found that its loss spurred congenital (existing prior to birth) malformations of the aortic valve which predispose individuals to AVD later in life. As with AVD, congenital malformations of the valve are strongly linked to patient sex in humans.
This work has furthered our understanding of why AVD progresses differently in men and women, and will aid in the development of novel treatment strategies for this disease (more effective and targeted pharmaceutical intervention).