Cardiovascular disease (CVD) remains the leading cause of death around the world and its incidence increases greatly with age in both males and females. However, the rate of CVD development increases significantly more in postmenopausal females. Our efforts are focused on identifying alternative strategies outside of hormone replacement therapy to mitigate CVD risk in aging women, and potentially men, as our approaches allow for the direct comparison of males and females and potential therapeutic targets that we identify may also aid in male CVD.
For these studies, we routinely utilize our state-of-the-art transgenic mouse models, in vitro molecular and cellular biology techniques, ex-vivo resistance vessel reactivity via wire myography, in vivo telemetric blood pressure measurements and in vivo cardiac and vascular imaging. Additionally, our laboratory also performs clinical studies examining vascular function in several populations. For these studies, we measure 1) microvascular function in the cutaneous circulation via laser Doppler flowmetry coupled with intradermal microdialysis and 2) arterial stiffness via applanation tonometry. Thus, we are a truly translational laboratory with studies spanning from the bench to the mouse to the human.
Current projects include:
The DuPont lab is interested in sex-specific mechanisms that contribute to the development of arterial stiffness, specifically in the setting of aging. We have shown that females are protected through middle age compared to age-matched males and that they have a delayed but quick increase in arterial stiffness at older time points (18+ months). For these studies, we are specifically interested in the role of smooth muscle cell estrogen receptor alpha (SMC-ERα) and have created a novel SMC-specific ERα knockout mouse. Our current approaches are focused on determining the potential role of unliganded SMC-ERα (receptor un-bound to estrogen) in the development of arterial stiffness with aging in both females and males.
Angiotensin II is a peptide hormone that acts on 2 receptors (AT1 and AT2). Previous evidence has supported a protective role for the AT2 receptor, along with sex and aging differences in the function of this receptor in tissues outside of the vasculature. We are interested in the role of AT2 receptors in vascular aging and have measured the function of this receptor in mesenteric resistance arteries as well as large elastic arteries in our preclinical mouse models. We also utilized our clinical techniques to extend our preclinical findings to humans. We measured the cutaneous vasoconstriction response to angiotensin II in the presence and absence of an angiotensin II type 2 receptor blocker in healthy men and women to determine 1) is AT2 receptor function enhanced in young females and 2) if we block this receptor, do the females respond similarly to the males.
We are interested in the role that sex hormones and their receptors play in vascular function and disease states. Specifically, we are interested in examining the effects of gender-affirming hormone therapy on vascular function in transgender adults. For these studies, we are measuring 1) microvascular endothelial function via laser Doppler flowmetry coupled with intradermal microdialysis and 2) arterial stiffness via applanation tonometry. Our long-term goal is to identify potential therapeutic targets that aid in retaining gender-affirming hormone therapy benefits while mitigating any potential increase in CVD risk due to such therapies.
Lab members
- Casey Turner, PhD, Postdoctoral Fellow
- Karla de Oliveira, PhD, Postdoctoral Fellow
- Jennifer Dupont, PhD, Principal Investigator
Previous members
- Rachel Kenney, BS, current position: MBA student at Oregon State University
- Jennifer Vorn, BS, current position: Research Scientist II, Novartis
