Published February 2, 2023
Yongho Bae, PhD, assistant professor of pathology and anatomical sciences, has been awarded a five-year, $2.9 million grant from the National Heart, Lung and Blood Institute to continue his research into the effects of arterial stiffness on cardiovascular disease.
Bae is principal investigator on the study titled “Biomimetic Vascular Matrix for Vascular Smooth Muscle Cell Mechanobiology and Pathology” that aims to identify potential new therapeutic targets for the treatment of cardiovascular disease.
He was awarded a R56 grant totaling $639,543 in 2022, which provided funding for the first year of the study. Subsequent years will be funded by an R01 grant totaling $2.27 million.
Arterial disease is diagnosed in 17 million Americans each year, with annual national health care costs estimated at more than $140 billion, according to the American Heart Association.
Two major types of arterial disease, atherosclerosis and arteriosclerosis, are characterized by narrowing and stiffening of the arteries. The main causes of neointima narrowing, or thickening, are abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) and the associated deposition of extracellular matrix (ECM) proteins.
Arterial stiffness is a predictor of cardiovascular diseases; however, the underlying mechanism by which arterial stiffening promotes abnormal VSMC function associated with neointima formation in the vessel wall is largely unknown, according to Bae.
His research group focuses on the rapidly growing field of cellular mechanotransduction, specifically, the role that mechanical forces play in regulating cellular function.
“This research explores the novel roles of survivin, a member of the inhibitor of apoptosis protein family, as a key regulator of stiffness-mediated VSMC phenotypes, neointima formation and arterial stiffening,” he says.
The researcers will employ in vitro porcine aorta decellularized extracellular matrix-based experimental systems, sophisticated single-cell-based analyses, and a mouse model system to examine the interactions between VSMCs and the pathological vascular environment and to identify potential new therapeutic targets for the treatment of cardiovascular disease.
Specific aims of the research are to:
Bae says work on the grant will bring together investigators with unique expertise to elucidate how a pathological ECM environment impacts VSMC mechanobiology and contributes to arterial stiffening by using a physiologic 3D in vitro system and an in vivo model system for the overall goal of identifying new targets and therapies for the treatment of cardiovascular disease.
The team members, their roles and their areas of expertise are: