Date of Award
Doctor of Philosophy (PhD)
Cardiovascular diseases (CVDs) are the leading cause of death worldwide in males (XY) and females (XX). Prior to menopause, females have a relative protection against serious cardiac pathologies compared to age-matched males. This phenomenon is widely attributed to the ovarian hormone estrogen. Unfortunately, hormone replacement therapy to maintain estrogen levels in postmenopausal females has overall adverse effects, and it is not recommended for long-term use or as a preventative measure for eCVDs. A major driver of CVDs, specifically heart failure, is cardiac fibrosis: the continued buildup of scar tissue that reduces the heart’s ability to pump. There are currently no FDA-approved therapies to specifically target cardiac fibrosis, and the five-year survival rate for patients diagnosed with heart failure is typically under 50%.
Recent studies exhibit the potential of estrogen to decrease the fibrotic response of cardiac fibroblasts, the cells responsible for the progression of fibrosis. However, most of these studies were conducted on tissue culture plastic (TCP) and/or with pooled male and female neonate rat CFs, limiting their clinical relevance. The goal of this dissertation is to expand our understanding of the sex-specific signaling of estrogen within CFs using in vitro and in silico techniques to identify potential sex-specific dimorphisms in regulatory signaling that will allow for the creation of novel treatments of cardiac fibrosis that mimic estrogen’s therapeutic abilities while negating its adverse systemic effects.
Biological sex impacts the presentation, prognosis, and severity of many conditions. Yet, females have been historically underrepresented in clinical trials and experimental studies, resulting in health inequities that disproportionately affect women. Literature has shown that women are more likely to include female samples in their study design and report sex-disaggregated data. However, they have been consistently underrepresented in STEM fields. Increasing the number of female scientists will aid in shrinking the gender data gap, which will help elucidate our understanding of the sex-specific differences of various diseases and biological functions. In addition to my in vitro and in silico initiatives, I have developed in classroom techniques utilizing inclusive pedagogy strategies that specially target female students with an aim to increase their STEM self-efficacy and identity. These in vitro, in silico, and in classroom techniques are designed with the intention of fostering a more inclusive and equitable approach to healthcare.
Watts, Kelsey, "Using in vitro, in silico, and in-Classroom Techniques to Address the Gender Data Gap in Health Care" (2022). All Dissertations. 3067.
Author ORCID Identifier