Gaining a better understanding of cardiovascular disease and stroke requires a team effort. Cardiologists, cell and molecular biologists, geneticists and other specialists are all needed.
The scientists profiled below demonstrate the multidisciplinary nature of Einstein cardiology today.
Richard N. Kitsis, M.D.
Director, Wilf Family Cardiovascular Research Institute
Dr. Gerald and Myra Dorros Professor of Cardiovascular Disease
Dr. Kitsis has been fascinated by cell death for nearly two decades, and with good reason. "Cell death is crucial to the field of cardiology," said Dr. Kitsis. “It helps to explain why heart attacks kill some people and can cause heart failure in those who survive."
Dr. Kitsis and his team are exploring how cell death mechanisms like necrosis interact with apoptosis to damage the heart. Additionally, they have focused on a protein called apoptosis repressor with caspase recruitment domain (ARC). This protein, said Dr. Kitsis, "seems to be at a nexus where cardiac muscle cells make a lot of decisions about whether to live or to die."
By gaining a better understanding of the cell death mechanisms linked to ARC, Dr. Kitsis hopes to develop therapies for heart attack and heart failure — the final stop in the long journey from bench to bedside. "Our goal," he said, "is to improve cardiovascular health in our families, our neighbors and the world."
Thomas V. McDonald, M.D.
Professor, Departments of Medicine (Cardiology) and
Why does the heart sometimes stop pumping? Dr. McDonald and his colleagues are examining the role of protein mutations in several forms of sudden death. A notable example is long QT syndrome, a hereditary disorder of the heart’s electrical rhythm that can occur in otherwise healthy people and is potentially fatal.
"Once we understand how inherited mutations put one at risk for sudden death, we’ll be in a better position to keep people alive through drugs or by changing their behaviors," said Dr. McDonald. The team might, for example, advise at-risk people to avoid strenuous exercise, roller coasters or alarm clocks, since they could trigger a fatal arrhythmia.
So far, researchers have identified at least 12 genes that may harbor mutations that lead to long QT syndrome. "Most genes that carry these mutations are involved in making ion channels," explained Dr. McDonald. "When ions are out of balance, you have a heart rhythm disturbance."
Dr. McDonald serves as codirector of the Montefiore-Einstein Cardiogenetics Program, which provides one-stop help for families affected by sudden unexpected death syndrome, sudden infant death syndrome and other cardiac rhythm disturbances.
Bernice E. Morrow, Ph.D.
Sidney L. and Miriam K. Olson Professor in Cardiology;
Director, Division of Translational Genetics, Department of Genetics
The causes of congenital heart defects—present in about 1 percent of live births—are largely unknown, but most are likely due to a combination of genetic and environmental factors. To gain insights into genetic causes, Dr. Morrow and her colleagues study a human birth defect syndrome known as velo-cardio-facial syndrome (VCFS)/DiGeorge syndrome (DGS).
VCFS/DGS results from a deletion of 40 genes on one of two copies of chromosome 22 (22q11.2). The most common heart defect in patients is tetralogy of Fallot—a hole between the heart’s ventricles, obstruction of blood flow to the lungs, an out-of-place aorta and a thickened right ventricular wall.
Dr. Morrow has studied a mouse model of VCFS/DGS and found that one gene in particular, called TBX1, is most vital for normal heart development. The next step is to identify the defect-producing molecular changes that occur when TBX1 is missing, which could lead to gene therapy. Until then, "when ultrasound in pregnancy reveals a suspected heart defect of this type, we can test the 22q11.2 region for a deletion in amniotic fluid or fetal blood," said Dr. Morrow. "Having a team of doctors on hand at the birth can then give the newborn the best outcome possible."
Nicholas E. S. Sibinga, M.D.
Associate Professor, Departments of Medicine (Cardiology) and of Developmental & Molecular Biology
Smoking, high blood pressure and a high-fat diet are well-known risk factors for atherosclerotic heart disease—the most common form of the disease, in which arteries eventually become blocked. “But we now recognize that atherosclerosis is not simply a passive process in which fat accumulates and clogs up the artery,” said Dr. Sibinga. “Instead, artery damage results from a very active inflammatory process.” Inflammation can even cause arteries to thicken and stiffen without fat buildup—a condition called arteriosclerosis—which can set the stage for a heart attack or stroke as effectively as fat buildup can.
Dr. Sibinga and his laboratory colleagues focus on restenosis, the re-narrowing of arteries—which often occurs after arteries have been widened by balloon angioplasty. “We’ve identified new proteins activated after vascular injury, and our findings suggest that these proteins or protein fragments may be useful as therapies for controlling inflammation and other activities that occur within the walls of blood vessels,” said Dr. Sibinga. He will soon be testing these proteins in animals, with the goal of developing new ways to prevent restenosis, heart attacks, and strokes.