A new study led by researchers at Massachusetts General Hospital (MGH) has identified a mechanism behind the increased cardiovascular inflammation that occurs after a heart attack.
US – In collaboration with scientists at the Massachusetts Institute of Technology (MIT), they also developed a potential strategy to suppress inflammation in atherosclerotic plaques.
Co-author Matthias Nahrendorf (Center for Biology Systems at MGH) said that they found that the activation of the sympathetic nerve fibers within the arterial lining, which occurs in response to a heart attack, causes an increased expression of adhesion molecules in endothelial cells lining atherosclerotic plaques. These molecules attract inflammatory white blood cells and cause the cells to adhere to the plates, raising the risk of another heart attack.
“We also found that we can turn off the expression of these adhesion molecules by means of RNA interference provided by nanoparticles,” added the researcher, whose work in animal models of heart disease is described in an article published in Science Translational Medicine.
A 2012 study published in Nature led by Nahrendorf was the first to show that an experimentally induced heart attack led both to increased generation of monocytes and other inflammatory cells as well as accumulation of cells in existing atherosclerotic plaques. These immune cells bind to and penetrate into endothelial cells through adhesion molecules on the surface of endothelial cells.
In the current study, a series of experiments using a mouse model with atherosclerosis revealed that the activity of the sympathetic nerve fibers within the aortas of animals was responsible for the increased expression of several adhesion molecules after heart attack.
Researchers tested if small interfering RNA (siRNA), which are directed precisely to the production of specific proteins could be used to reduce expression of adhesion molecules on endothelial cells. This was achieved through targeted nanoparticles at five molecules adhesion that are known to be expressed at sites of arterial inflammation.
A 2011 study by Nahrendorf and several team members including ongoing research co-author Daniel Anderson, MIT had used siRNA nanoparticles to target a single inflammatory receptor protein.
A preventive and curative treatment
Addressing five adhesion molecules not only reduced the recruitment of inflammatory to the aortic plaques in animals immune cells, but also decreased the expression of inflammatory proteins called cytokines and enzymes which contribute to the breakdown of arterial plaque that triggers a heart attack.
Applying the treatment before an induced heart attack reduced subsequent inflammatory changes, while treatment after a heart attack reduced the recruitment of inflammatory cells in half and improved the recovery of heart function. A nanoparticle directed to a single adhesion molecule was significantly less effective.
Nahrendorf said there is no current cardiovascular therapy directed the recruitment of immune cells in the plates, although it is the main contributor to future ischemic events, caused by a cut of the blood supply. He hope we this approach it can help ‘cool’ inflammation in patients with ischemic organ injury, protecting heart patients of a second heart attack and help heart recover. The next step is to try this method in larger animals and confirm its safety before it can be evaluated in human patients, he concluded.