Strides Made Toward a Genetically Engineered Way of Treating Arrhythmias
Richard B. Robinson, Ph.D., professor of pharmacology, and collaborators at Columbia and Weill Medical College of Cornell University have recently published in The Journal of Physiology (and highlighted in two editorials in the same issue) results of studies advancing the field of biological pacemakers, which may one day render conventional electro-mechanical pacemakers an outmoded way of treating prevalent and persistent heart conditions. The study explores ways to optimize through mutagenesis and then validate in a cell culture system, the use of a specific gene family, the HCN (Hyperpolarization-activated Cation Channels) pacemaker family, for biological pacing. This is part of a long standing collaborative effort between labs and Columbia and Stony Brook University to use gene and cell therapies to treat cardiac arrhtyhmias.
Drugs Similar to One in Trials for Heart Disease May Slow Muscle Loss in Most Common Form of Muscular Dystrophy
Based on a striking similarity between heart disease and Duchenne muscular dystrophy, Dr. Andrew Marks, chair of the Department of Physiology & Cellular Biophysics and Clyde and Helen Wu Professor of Molecular Cardiology, and colleagues have discovered that a new class of experimental drugs for heart failure may also help treat the fatal muscular disorder. This study found that the muscle cells affected in both diseases have sprung the same microscopic leak that ultimately weakens skeletal muscle in Duchenne and cardiac muscle in heart failure. In Duchenne, the leak lets calcium slowly seep into skeletal muscle cells, which are then damaged from excess calcium. In people with chronic heart failure, a similar calcium leak continuously weakens the force produced by the heart and also turns on a protein-digesting enzyme that damages its muscle fibers. Dr. Marks hypothesized that a new class of experimental drugs developed at CUMC, which he designed to plug the leak in the heart; could also work for Duchenne. The drugs, when given to mice with Duchenne, dramatically improved muscle strength and reduced the number of damaged muscle cells. Though the new drugs are not FDA-approved or currently available for Duchenne patients, a similar drug that was used in the Duchenne study is undergoing Phase I safety trials, and later this year trials will begin for heart failure.
Cardiac Stent Patients with Diabetes May Benefit from Additional Drug that Counteracts the Effects of Leptin
While drug-eluting stents reduce the chance coronary arteries will become blocked again, clogged stents are more common in diabetic patients than in the general population. About 250,000 Americans with diabetes receive drug-eluting stents every year. A hormone commonly associated with obesity – leptin – may be partly responsible, according to recently published research in the Proceedings of the National Academy of Sciences by Andrew Marks, M.D., chair of physiology & cellular biophysics and Clyde and Helen Wu Professor of Molecular Cardiology, and Steven Marx, M.D., associate professor of medicine and pharmacology. The study found that leptin, at the elevated concentrations frequently found in patients with diabetes, stimulates the growth of cells responsible for clogging stents.
Surgical Intervention to Treat Severe Hypertension Beginning to Show Results in Clinical Trial -
Implanted Device Causes Body to Naturally Lower Blood Pressure
CUMC faculty are leading a multi-center, 300-patient trial to test the efficacy of the FDA-approved Rheos Baroreflex Hypertension Therapy System. This system, which is surgically implanted under the skin in the neck, electronically stimulates receptors in the carotid sinus, the area located at the bifurcations of the carotid arteries that are responsible for regulating blood pressure. While cardiologists have focused on alleviating hypertension and the myriad of health problems caused by this condition with drugs, there are many patients whose extreme hypertension will not respond to medication or changes in lifestyle. "One-third of the world's population is hypertensive, and only one-third of those people can only control their hypertension with the help of drugs,” says Dr. Daichi Shimbo, Assistant Professor in the CUMC Center for Behavioral Cardiovascular Health and the medical principal investigator for the multi-center trial. "There is a vast segment of the hypertensive population that could potentially benefit from surgically intervening to alter the way baroreceptors function." "The system is designed to work by stimulating the baroreceptors in the carotid sinus to make it appear as if patients are more hypertensive than they really are, forcing the body to respond and lower blood pressure," said Thomas Pickering, M.D., director of the Center for Behavioral Cardiovascular Health, and the national principal investigator of the trial. "For patients who have been unsuccessful at lowering extremely high blood pressures with the current pharmacological therapies, this device may be an invaluable option." Also involved in the study was E. Sander Connolly Jr., M.D., CUMC Associate Professor of Neurological Surgery.
Presence of Gum Disease May Help Dentists and Physicians Identify Those at Increased Risk for Cardiovascular Disease
Individuals reporting a history of periodontal disease were more likely to have increased levels of inflammation, a risk factor for heart disease, compared to those who reported no history of periodontal disease, according to an American Journal of Cardiology report. Led by investigators from Columbia University Medical Center and NewYork-Presbyterian Hospital, the findings suggest that persons with increased levels of inflammatory markers associated with a higher risk of cardiovascular disease might be identified by asking about oral health history. To examine whether oral health history and inflammatory markers associated with cardiovascular disease were linked, the investigators followed participants in the National Heart, Lung and Blood Institute (NHLBI) Family Intervention Trial for Heart Health (F.I.T. Heart), an ongoing national trial led by principal investigator Lori Mosca, M.D., M.P.H., Ph.D., professor of medicine at Columbia University College of Physicians and Surgeons and director of preventive cardiology at NewYork-Presbyterian Hospital/Columbia University Medical Center. Dr. Mosca says, "Our finding is novel because it suggests the dentist and oral health exam may be the latest weapon in identifying persons at risk of cardiovascular disease, our nation's number one killer." Co-authors included John T. Grbic, DMD, MS, MMSc, professor of clinical dental medicine at the Columbia University College of Dental Medicine and Heidi Mochari, M.P.H., R.D., director of nutrition for the Preventive Cardiology Program at Columbia University College of Physicians and Surgeons.
Columbia University Medical Center Announces 2008 Katz Prizes in Cardiovascular Research
Columbia University Medical Center announced the winners of the 2008 Katz Prizes in Cardiovascular Research. Lewis Katz, entrepreneur and philanthropist, created these prizes in 2006 to recognize outstanding contributions in cardiovascular research, by both senior scientists and young investigators working on pertinent questions related to cardiovascular health. The senior scientist prize was awarded to the research team of Christine E. Seidman, M.D., and Jonathan G. Seidman, Ph.D., both of Harvard University, two internationally renowned researchers who have been credited with discovering many genetic causes of cardiac disorders. The young investigator prize recognized Andrew J. Einstein, M.D., Ph.D., of Columbia University Medical Center, a cardiovascular researcher studying computed tomography angiogram (CTA), a new, non-invasive imaging technique used to assess levels of calcium and fatty deposits in the coronary arteries.
Intervention Trial to Improve Heart Health in Relatives of Hospitalized Heart Disease Patients
Lori Mosca, M.D., Ph.D., M.P.H., professor of medicine at Columbia University Medical Center and director of preventive cardiology at New York-Presbyterian Hospital, presented the results of a recently completed randomized controlled trial at the American Heart Association's 2008 Scientific Sessions. She reported that relatives of hospitalized heart disease patients improved their lifestyle and lowered some risk factors after participating in a hospital-based systems approach to health screening and lifestyle counseling. "Having a family member hospitalized with an acute cardiovascular event might represent a very unique 'motivational moment' in which relatives would be willing to take personal action to improve their own lifestyles and lower their cardiovascular risk." said Dr. Mosca.
Drive Begun to Foster Advances In Cardiovascular Research
The Columbia University Medical Center is already renowned internationally for its excellence in cardiovascular research, especially in the areas of atherosclerosis, arrhythmia, and heart failure. Now, in an effort to support growth and expansion in basic and translational cardiac research, as well as boost collaborations, the College of Physicians and Surgeons has launched the Cardiovascular Research Initiative (CVRI). The CVRI will enhance existing programs and strengthen capabilities in cardiovascular genetics, vascular biology, and developmental biology.
Cardiovascular Research Initiative symposiumJune 17, 2008
This new study shows that the fatigue that marathoners and other extreme athletes feel at the end of a race is caused by a tiny leak inside their muscles that probably also saps the energy from patients with heart failure. The leak - which allows calcium to continuously leak inside muscle cells - weakens the force produced by the muscle and also turns on a protein-digesting enzyme that damages the muscle fibers. The leak, which was previously discovered by Dr. Andrew Marks and colleagues in the muscles of animals with heart failure, was present in the muscle of mice after an intense three-week daily swimming regimen and in human athletes after three days of daily intense cycling. This new study found that an experimental drug developed by the researchers alleviated muscle fatigue in mice after exercise, suggesting that the drug also may provide relief from the severe exhaustion that prevents patients with chronic heart failure from getting out of bed or fixing dinner. The results were published in the online edition of the Proceedings of the National Academy of Sciences on February 11, 2008.
CUMC Press Release (Feb 11, 2008)
New York Times Article (Feb 12, 2008)
2007 Katz Prizes in Cardiovascular Research
James T. Willerson, M.D., FACC, president of The University of Texas Health Science Center at Houston and a leading cardiology researcher, is recognized by the Lewis Katz Visiting Professorship in Cardiovascular Research for excellence in cardiovascular research and education.
Thomas G. Diacovo, M.D., assistant professor of pediatrics and pathology and director of research for the neonatology and critical care medicine divisions within the Department of Pediatrics at the College of Physicians and Surgeons is awarded the Lewis Katz Cardiovascular Research Prize for a Young Investigator, which recognizes a junior faculty member at Columbia University Medical Center with great promise for contribution to the study of cardiovascular disease.
Clyde and Helen Wu Distinguished Lecture Series
The inaugural Clyde and Helen Wu Distinguished Lecture Series took place on Dec. 10 with a presentation by Robert Lefkowitz, M.D., the James B. Duke Professor of Medicine at Duke University Medical Center and Howard Hughes Medical Institute investigator. Dr. Lefkowitz, P&S’66, is a pioneer in the field of molecular cardiology. The series is sponsored by the Clyde and Helen Wu Center for Molecular Cardiology, directed by Andrew Marks, M.D., the Wu Professor of Molecular Cardiology and chairman of the Department of Physiology. The Center was created in 2006 with a gift from University trustee and longtime supporter Clyde Wu, M.D., P&S’56, and his wife, Helen. Dr. Wu is a cardiopulmonary specialist at Wayne State University College of Medicine.
Department of Pharmacology
"Rubor, Calor, Dolor, et NCor; New Repression Pathways that Regulate Inflammation"
Christopher C. Glass M.D., Ph.D.
Professor of Medicine, Cellular and Molecular Medicine
University of California, San Diego
Clyde and Helen Wu Center for Molecular Cardiology
"A Brief History of Seven Transmembrane Receptors: New Approaches to Drug Therapy"
Robert J. Lefkowitz, M.D.
James B. Duke Professor of Medicine
Investigator, Howard Hughes Medical Institute
Duke University Medical Center
2006 Katz Prizes in Cardiovascular Research
Eugene Braunwald, M.D., Distinguished Hersey Professor of Medicine at Harvard Medical School and Chairman of the TIMI Study Group at the Brigham and Women's Hospital, is the inaugural recipient of the Lewis Katz Visiting Professorship in Cardiovascular Research. A major force in the field of cardiology for the past half century, Dr. Braunwald's findings relating to cholesterol and coronary artery disease have impacted the care of millions of patients. In fact, the living Nobel Prize winners in medicine voted Dr. Braunwald the person who has contributed the most to cardiology in recent years. He also holds the special honor of being the first cardiologist elected to the National Academy of Sciences of the United States.
Geoffrey S. Pitt, M.D., Ph.D., Esther Aboodi Assistant Professor of Medicine and Pharmacology in the Center for Molecular Cardiology at CUMC, is the recipient of the Lewis Katz Cardiovascular Research Prize for a Young Investigator. This prize recognizes a junior faculty member at the Medical Center who holds great promise for contribution to the study of cardiovascular disease. Dr. Pitt is conducting groundbreaking work in the study of the often fatal disturbances of the heart's normal rhythm.
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