A New Factor in Heart Disease
Researchers have identified a mechanism in the body that’s linked to a surge in cardiovascular inflammation following a heart attack.
The scientists also developed a possible strategy for suppressing inflammation within atherosclerotic plaques. It is the first approach, they said, that targets the immune system’s role in cardiovascular diease.
The work, by researchers from Massachusetts General Hospital (MGH) and the Massachusetts Institute of Technology (MIT), was described in a Science Translational Medicine paper.
The investigation used animal models.
“We found that activation of sympathetic nerve fibers within the arterial lining, which takes place in response to a heart attack, leads to increased expression of adhesion molecules on the endothelial cells lining atherosclerotic plaques. Those molecules both attract inflammatory white blood cells and cause those cells to stick to the plaques, increasing the risk for another heart attack,” says Matthias Nahrendorf, MD, PhD, of the MGH Center for Systems Biology, co-senior author of the report. “We also found that we can shut off the expression of those adhesion molecules by means of nanoparticle-delivered RNA interference.”
A 2012 study led by Nahrendorf was the first to show that an experimentally induced heart attack led both to the increased generation of monocytes and other inflammatory cells and to the accumulation of those cells in existing atherosclerotic plaques. These immune cells attach themselves to and penetrate within endothelial cells by means of adhesion molecules on the surface of endothelial cells. In the current study, a series of experiments with a mouse model of atherosclerosis revealed that activity of sympathetic nerve fibers within the animals’ aortas was responsible for the increased expression of several adhesion molecules after a heart attack.
The investigators then tested whether small interfering RNA (siRNA), which precisely targets the production of specific proteins, could be used to reduce the expression of adhesion molecules on endothelial cells. This was accomplished by means of nanoparticles targeting all five adhesion molecules known to be expressed at sites of arterial inflammation. A 2011 study by Nahrendorf and several members of the current research team – including co-senior author Daniel Anderson, PhD, of MIT – had utilized siRNA nanoparticles to target a single inflammatory receptor protein.