Doctoral Defense - Leah Terrian

The Department of Biomedical Engineering

Michigan State University

Ph.D. Dissertation Defense

October 3, 2025 at 12 pm EST

Life Science Bldg B448

By: Leah Terrian

Advisor: Dr. Sudin Bhattacharya

Abstract: Cardiovascular diseases affect over half a billion people worldwide and in 2021 accounted for the loss of 20.5 million lives, nearly a third of all deaths globally. One of the leading risk factors for developing cardiovascular disease is high blood pressure, also known as hypertension. Hypertension is a commonly diagnosed condition, currently afflicting nearly half (47.7%) of all U.S. adults. More than 90% of hypertension cases, termed primary or essential hypertension, do not have a known cause. It has recently been shown that a layer of fat tissue that surrounds most blood vessels, aptly named perivascular adipose tissue (PVAT), plays an important role in blood pressure regulation. Once thought to serve only as structural support, it is now known that PVAT secretes a variety of vasoactive factors and can modulate vascular tone. Yet, its cellular and molecular landscape, particularly in the context of hypertension, remains poorly understood. In this dissertation, we take a closer look at this intriguing blood vessel layer using single-nuclei RNA sequencing and PVAT from the thoracic aorta of Dahl salt-sensitive rats. First, we build a PVAT cell atlas, revealing which cell types make up PVAT, the proportions of those cell types, and the genes each of those cells are expressing. Then we compare our PVAT cell atlas to a brown adipose tissue cell atlas to uncover the factors unique to PVAT. Next, we examine PVAT in the context of health versus disease by comparing samples from rats with normal and elevated blood pressure. Finally, we describe how we are advancing our methodology to improve nuclei isolation from white adipose tissue-like PVAT, thereby enabling future single-cell studies of additional PVAT depots. Together, these findings provide a clearer picture of PVAT, how it is unique relative to other adipose tissues, and how it changes under hypertensive conditions. By advancing both biological insight and methodology, this work establishes a foundation for exploring PVAT as a therapeutic target for hypertension.