In a surprising result, a blood vessel whose internal “clock” has been disrupted will continue to develop vascular disease even when transplanted into a healthy host, researchers at Georgia Health Sciences University reported today.
The findings might shed light on why some transplants fare better than others and could open a whole new field of study, a GHSU researcher said.
Published in the Proceedings of the National Academy of Sciences, Dr. R. Daniel Rudic and others in his lab at GHSU built on previous findings at the university about disruptions in the body’s internal clock.
Previous work had shown that not only does the body have a central “clock” that cycles up and down from day to night but individual cells, for instance in arteries, have their own internal clocks that respond to the central clock.
The central clock can get disrupted and lead to diseases such as arteriosclerosis, the hardening of arteries. But individual cells can also have their clocks disrupted and lead to disease.
To test this theory, the GHSU team led by Dr. Bo Cheng took blood vessels and transplanted them between mice that were normal and mice that had the “clock” genes knocked out or disrupted. Blood vessels from a healthy mouse transplanted into mice with a bad central clock continued to behave like normal, healthy blood vessels. But blood vessels with a bad clock that were transplanted into healthy mice went on to develop arteriosclerosis, the researchers found.
“You actually have to have clock dysfunction at the level of the tissue to incur disease, which is surprising to us,” Rudic said. “But it points to the importance of these tissue clocks as well.”
The research could perhaps help explain studies that found that the time of day liver transplants were performed helped influence the outcomes, with night surgeries faring worse, the study said. While more work needs to be done, the study suggests that timing could have an influence on transplant success in a few ways, Rudic said.
“It could be the time at which you harvest the organ,” he said. “It could be also the time at which you do the surgery to transplant the organ.”
It might also be the way in which the organ is stored that could be influencing the tissue clocks, Rudic said. It just has not really been explored yet, he said.