Cardiovascular disease is a leading cause of death in the United States and the contributing factor for one in every four deaths. An improved understanding of the mechanisms behind atherosclerosis, a common contributor to cardiovascular disease, may help guide new therapeutic strategies to combat this deadly disease.

University of Pittsburgh graduate student Abigail Allen—who works in the laboratory of McGowan Institute for Regenerative Medicine affiliated faculty member Partha Roy, PhD, Associate Professor of Bioengineering, Cell Biology, and Pathology at the University of Pittsburgh—received an F31 award from the National Institutes of Health for her work that examines the effect of actin-binding protein Profilin-1 (Pfn1) perturbation in atherosclerosis. Her studies involve taking a close look at angiogenesis and how Pfn1 may play an important role in its function.

“Angiogenesis is the process in which new blood vessels sprout from pre-existing vasculature, and it is facilitated by complex interaction between endothelial cells (EC), extracellular matrix (ECM) and various stromal cells (immune cells, fibroblasts),” Ms. Allen explained. “This process is central to both normal physiology and life-threatening pathologies, like cancers, atherosclerosis, or diabetic retinopathy.”

In addition to facilitating nutrient delivery, new vessel formation from angiogenesis also promotes infiltration of immune cells into the vascular system during inflammation and diseases involving inflammation.

“Actin cytoskeleton remodeling in EC not only plays pivotal role in cellular restructuring, cell motility and sprouting angiogenesis, but is also important for features that impact vascular infiltration of immune cells, such as regulation of EC barrier function and EC-immune cell interactions,” Ms. Allen added.

Studies from the Roy Lab have demonstrated that actin-binding protein Pfn1, an important regulator of actin cytoskeletal dynamics, is an indispensable endothelial mediator of angiogenesis in both physiological and abnormal settings.

Other studies report that in preclinical setting of atherosclerosis, an overall decrease in Pfn1 expression—by modifying the gene at the embryonic level—leads to less vascular infiltration of pro-atherogenic immune cells, specifically macrophages. This effect reduces the disease burden.

“These taken together with my preliminary findings that endothelial Pfn1 depletion dramatically alters the circulating levels of immune-modulatory cytokines in vivo, underscore the importance of endothelial Pfn1 function in vascular biology with potential impact on vascular-immune cell interactions,” Ms. Allen said.

Illustration:  Roy Lab (Allen)/McGowan Institute for Regenerative Medicine (Roy).

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University of Pittsburgh Swanson School of Engineering News Release