Neointimal hyperplasia is a well-documented remodeling of the innermost vascular layer after vascular interventions and is a significant clinical outcome for many, especially people who have undergone cardiovascular procedures. Proliferation and migration of vascular smooth muscle cells (SMCs) in the innermost layer of an artery or vein results in vascular wall thickening, which leads to the return of reduced vascular flow.
Anil Chauhan, MTech, PhD, professor in Hematology, Oncology and Blood & Marrow Transplantation, and his lab have narrowed in on a potential target for reducing neointimal hyperplasia after vascular insult. The fibronectin-splice variant containing extra domain A (Fn-EDA) is abundant in the arteries of patients with atherosclerosis and is associated with SMCs following vascular injury, particularly after stent implantation in the treatment of coronary artery disease. In a paper just published in the Journal of Clinical Investigation, Chauhan and colleagues demonstrate the expression of Fn-EDA near the neointima and areas surrounding the stent.
In a forthcoming Author’s Take video produced for JCI, lead author Manish Jain, PhD, postdoctoral research scholar, explains that although previous in vitro studies have demonstrated that Fn-EDA is a characteristic feature of synthetic SMCs, the specific role of SMC-derived Fn-EDA in the pathophysiology of neointimal hyperplasia is not completely understood.
Jain and colleagues generated novel endothelial and SMC-specific Fn-EDA-/- mice to test the role of different sources of Fn-EDA in SMC proliferation and neointimal hyperplasia. They also used human coronary artery specimens with an implanted bare metal stent, as well as wire-injured carotid arteries of genetically modified hyperlipidemic mice. They then examined isolated SMCs from both models to substantiate clinical relevance.
The team concluded that, following vascular injury, Fn-EDA is synthesized by proliferative SMCs, creating signals that may amplify the inflammatory microenvironment in the injury area, thereby promoting intimal hyperplasia. Targeting Fn-EDA via a blocking antibody may be a therapeutic option for treating patients after stent placement who are at risk for atherosclerosis.
In addition to Jain and Chauhan, other contributors from the University of Iowa included Drs. Nirav Dhanesha, Prakash Doddapattar, Mehul Chorawala, Manasa Nayak, and Steven Lentz.