Identification of Atherosclerotic Plaque-Building Circulating Cells Released After Joint Trauma
Abstract
Atherosclerosis, or “hardening of the arteries,” results when tough plaques build up on the insides of the blood vessels feeding the heart and can deprive the heart muscle of the oxygen that blood would carry, causing a heart attack. Such heart attacks resulting from atherosclerosis are 25 times more likely to occur immediately after orthopedic surgical operations, particularly hip replacements. These operations require direct open surgical fracture of the joints during their reconstruction and replacement, similar to the kinds of traumatic joint damage that can happen from falls, vehicle accidents, or Soldiers’ combat injuries. Could debris from a fractured joint or limb during an operation find its way into the bloodstream and directly build the plaque found on the patient’s arteries, thus making the arteries narrower and a heart attack more likely? We suspect that joint cells can cross the walls of the blood vessels and enter the bloodstream and can travel to atherosclerotic plaques on the walls of arteries, making the plaques bigger. Several pieces of evidence suggested to us why our speculation might be true. In addition to the higher risk of heart attack after joint surgeries, there is an apparent surge of bone-like cells found in the bloodstreams of adolescents, particularly after bone fracture. Further, we know, from looking at the joints of mice that have been injured that the walls of normal blood vessels are surrounded by cells that typically reside in cartilage and bone. Some of these cells appear as if they are ready to gain entry into the blood circulation. To find out if our suspicion that joint cells can travel through the blood to build plaques after joint injury is true, we have designed a study to offer definitive evidence to answer this question using objective and rigorous laboratory testing. First, we will study a kind of mouse that readily develops blood vessel plaques because of a missing gene. The plaques on the blood vessel walls of this kind of mouse are very easy to identify and study. We will look for increases in the numbers of joint cells that can be found in their vessels’ plaques after they suffer a joint injury compared to the similar information gained in same kind of mouse that is not injured. We anticipate that the number of joint cells in the plaques will be higher after these joint injuries, suggesting that the joint cells get there from debris shed into the bloodstream from the injured joint. Second, and almost simultaneously, we will use a system that labels limb-derived cells specifically. This will allow us to distinguish one cell’s lineage, or ancestry in the body, from another’s. We can tell whether a cell is derived from the limb cartilage or bone or from elsewhere, and we will employ this system to show that cells with limb ancestry reach the plaques. By analyzing how these limb joint cells make up a portion of the cells in the blood vessel plaque, we can then say as definitively as possible that cells with limb joint heritage help to build the blood vessel plaques. In order to ensure what we study is relevant in humans, we will then use tissue discarded from joint replacement surgeries. We will transplant human cells from the discarded tissue into the bloodstreams of the mice. We anticipate that these human cells will find their way into the plaques on the walls of the arteries of the mice, just like the cells of the mice did. If this is true, it means that human cells are capable of traveling from injured joints through the bloodstream and into the plaques on the walls of arteries this way and might explain why patients get heart attacks more often after joint injuries from trauma or surgery. This discovery would open the door to look for new ways to prevent heart attacks in joint injury and joint surgery patients, perhaps by blocking these cells from entering the plaques or even by preventing the release of the cells from the injured joints dur
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810119
Entities
People
- Hong Mei
Organizations
- Massachusetts General Hospital
- United States Army