Dr. Thomas S. Monahan, a surgeon at the Baltimore VA Medical Center, has successfully found a way to prevent intimal hyperplasia — or thickening within arteries — by identifying and successfully blocking a protein associated with the scarring process. His paper titled, “MARCKS Signaling Differentially Regulates Vascular Smooth Muscle and Endothelial Cell Proliferation through a KIS-, p27kip1- Dependent Mechanism,” in the Nov. 3 issue of the Public Library of Science (PLOS) Journals, could change the way heart disease is treated by possibly leading to the replacement of drug-eluting stents and drug-coated balloons.
In mouse studies, Monahan, the 2013 Wylie Scholar in Academic Surgery to Vascular Cures, found that the protein — myristoylated alanine-rich C kinase substrate (MARCKS) — causes the thickening or scarring process to occur in vascular diseases such as restenosis after bypass surgery. Using siRNA-mediated MARCKS knockdown, Dr. Monahan has proven that interruption of this pathway prevents the proliferative response seen after arterial reconstruction, but also increases the restoration rate of a normal blood vessel lining, or re-endothelialization.
“The scarring — or thickening of the innermost layer of the blood vessel — occurs when vascular smooth muscle cells first migrate to the intima and then proliferate at a high rate,” said Dr. Thomas Monahan, an attending vascular surgeon at the Baltimore VA Medical Center, a recipient of the VA Career Development Award, and an assistant professor of surgery at the University of Maryland School of Medicine. “This thickening within the vessels limits the durability of the original procedure by blocking the blood flow, in essence becoming a blockage itself, and it can lead to other things like thrombosis or clotting of the vessel.”
Intimal hyperplasia can limit the outcomes of original procedures such as bypass and angioplasty because the thickening or scarring within the arteries can itself cause blockages, and to counteract this outcome, drug-eluting stents and drug-coated balloons are used to try to circumvent or prevent the scarring. Unfortunately, these drug-coated agents also inhibit other cells from growing and cause increased bleeding complications. Currently, drug-eluting stents prevent the restoration of a normal blood vessel lining, and consequently patients who have these stents need to be on powerful blood-thinning medications indefinitely.
“This is a remarkable and potentially very important observation,” said Robin Pierson, professor of surgery at the University of Maryland School of Medicine and a staff surgeon at the Baltimore VA Medical Center. “Differentially targeting MARCKS in various compartments of the artery wall may eventually lead to new drug or gene therapy treatments for patients with atherosclerosis.”