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Research Highlights

Journey to the Center of a Blood Vessel

Key risk factors for heart attacks and strokes are high blood pressure and high blood cholesterol. Dr. Nicholas Sibinga is working to mitigate the blood vessel damage they cause.

Dr. Nicholas Sibinga wants to prevent two of America's leading killers: heart attacks and strokes. His strategy is to minimize blood vessel damage by deploying proteins that protect or repair smooth muscle cells in blood vessel walls.Nicholas Sibinga, M.D.Dr. Sibinga, an associate professor of medicine (cardiology) and of developmental and molecular biology, studies the earliest effects of high blood pressure and high cholesterol at the molecular level. High blood pressure and high blood cholesterol affect arteries differently. The damage from high blood pressure starts as inflammation that can lead to hardened, thickened, inflexible arteries (arteriosclerosis); high blood cholesterol leads to artery-clogging fat buildup (atherosclerosis). Dr. Sibinga focuses on proteins involved in repairing cells that are in the early stages of damage from high blood pressure and cholesterol. "By the time arteries are blocked, you already have a serious problem," says Dr. Sibinga, a member of Einstein's Wilf Family Cardiovascular Research Institute. His findings could lead to new therapies that would save many lives.

Meet the Proteins

Dr. Sibinga is especially interested in proteins that are potent helpers and healers of the smooth muscle cells in the blood vessel walls:

  • Fat1 cadherin. Levels of Fat1 cadherin, found in cell membranes, increase significantly after vascular injury. The protein receives chemical signals from nearby cells injured by the chronic inflammation of atherosclerosis. It then controls the growth and movement of individual cells to orchestrate vascular repair.
  • Atrophins. Levels of atrophin proteins also rise significantly after vascular injury. Atrophins bind to Fat1 cadherin to steer just the right number of newly made smooth muscle cells to weak or damaged areas of the vessel wall. Mouse studies show that when smooth muscle cells produce too little Fat1, the repair process goes haywire and too many smooth muscle cells are laid down in the injured area of the blood vessel wall—leading to a dangerous thickening.
  • Beta-catenin. This protein, which also binds to Fat1, helps injured smooth muscle cells survive during repair by turning on specific survival genes that help the cells cope with vascular damage.

These proteins may be especially useful in treating restenosis and post-transplant arteriosclerosis.

Wilf Family Cardiovascular Research Institute Newsletter 2013
This article was originally published in the winter/spring 2013 Wilf Family Cardiovascular Research Institute newsletter.
Restenosis: Balloon angioplasty and stenting are used to widen coronary arteries narrowed by heart disease. But up to 40 percent of the time, these widened arteries renarrow—a process known as restenosis. "Once we understand the signals by which Fat1 promotes migration of cells to the site of a vascular injury, it could lead to a new generation of stents coated with the protein, which will directly contact smooth muscle cells and speed the body's natural healing process," says Dr. Sibinga, also an attending physi­cian in the division of cardiology at the Montefiore Einstein Center for Heart and Vascular Care. Mobilizing atrophins and beta-catenin also could help the repair effort.

Post-transplant arteriosclerosis: Within 10 years of receiving a heart transplant, about half of the patients experience thickening of the coronary artery walls. This artery thickening reduces blood supply to the heart and can lead to heart failure. We already know that Fat1 is turned on in trans­plant arteries as well as in other vascular injury settings and could be a potential therapy. Dr. Sibinga is studying another protein, colony stimulating factor 1 (CSF-1), which causes inflammation in blood vessel walls. In experiments, mice that can't produce CSF-1 don't develop transplant arteriosclerosis. This finding suggests a new prevention strategy in humans: several investiga­tional cancer drugs that inhibit CSF-1 may also prevent transplant arterioscle­rosis. (Less is known about atrophins' and beta-catenin's role in transplant arteriosclerosis.)

Meanwhile, when Dr. Sibinga coun­sels patients about heart health, he emphasizes the role of inflammation and the importance of taking statins.

Posted on: Friday, August 23, 2013

Questions and Answers

Statins counteract the fat buildup that can lead to heart attacks and strokes. Do they also fight inflammation?

Statins lower LDL cholesterol (low-density lipoprotein cholesterol, sometimes called "bad cholesterol") effectively, but they also have beneficial anti-inflammatory effects. "This combination of cholesterol lowering and inflammation quenching makes statins particularly useful medications," says Dr. Sibinga.