“One of the most important features of heart and vascular research at UCSF has always been that it includes people from a range of departments and disciplines spanning basic science and patient-based work,” says Shaun Coughlin, MD, PhD, director of the world-renowned Cardiovascular Research Institute (CVRI) at UCSF. “That enables us to bring together investigators with different skill sets and knowledge bases to solve problems.”
Lisa Wilsbacher, MD, PhD, and Shaun Coughlin, MD, PhD
Established in 1958, CVRI is the source of several medical breakthroughs that evolved from this approach: from proving that drugs known as ACE inhibitors extend life for congestive heart failure patients to discovering a procedure that can cure some heart rhythm problems without surgery.
“CVRI investigators like John Clements and William Tooley, who developed a therapy for infant respiratory disease that resulted in the largest drop in infant mortality in the United States in modern history, set the tone by finding the molecular explanation for a clinical problem and then developing an effective therapy,” says Coughlin.
Research Across Disciplines
Ongoing UCSF basic science and clinical research involves teams of experts who represent an array of disciplines and are investigating numerous heart and vascular disorders, including:
- Blood clots: Coughlin led a CVRI team that cloned and characterized a key sensor that regulates blood clotting. His work has enabled the development of a potentially revolutionary class of clot-preventing drugs that now are in large-scale clinical trials and could reduce the risks of heart attack or stroke.
- Heart attack and stroke: CVRI investigators John Kane, MD, PhD, and Mary Malloy, MD, have identified more than 200 genes associated with increased risk of heart attack or stroke. The genes could point the way toward new strategies to reduce the risk of these disorders, which are the country’s leading causes of death and disability. Their genetic studies are continuing, along with other work that has led to discoveries of previously unrecognized metabolic disorders that underlie cardiovascular disease. The team sees patients with disorders of lipoproteins in the UCSF Lipid Practice, where global risk for atherosclerotic disease is also assessed.
- Congenital heart disease: By looking at how tissues and organs develop in baby mammals, researcher Brian Black, PhD, is enhancing the understanding of how illnesses like congenital heart disease develop. Such work could lead to novel ways to repair and even regenerate damaged organs, including the heart and blood vessels.
- High cholesterol: Marguerite M. Engler, RN, PhD, of the UCSF School of Nursing, is testing whether a low-cholesterol diet alone, or together with heart-protective supplements or vitamins, will improve the ability of blood vessels to dilate in children and adolescents who have high cholesterol. In the EARLY (Endothelial Assessment of Risk from Lipids in Youth) trial, participants and their parents work with nutritionists to learn about heart-healthy diets. Researchers also will evaluate the effects of the dietary supplements on cholesterol markers in the blood.
Atrial Fibrillation and Genetic Arrhythmias
Jeffrey Olgin, MD, chief of the UCSF Division of Cardiology, and his colleagues in the Cardiac Electrophysiology and Arrhythmia Service are conducting a large research project to understand the causes of, develop novel treatments for and prevent the type of irregular heartbeat called atrial fibrillation. This disorder affects more than 2 million Americans, and puts people at increased risk for conditions that include stroke and congestive heart failure.
Mitochondrion, a membrane-enclosed organelle found in most cells.
Another important research effort is focusing on genetically based arrhythmias that can put patients at risk for sudden cardiac death. UCSF’s Melvin Scheinman, MD, a world-respected pioneer in arrhythmia treatment, has created the Comprehensive Genetic Arrhythmia Program, which includes both a basic science and clinical research component.
“Our research should improve our ability to recognize, diagnose and treat these complex genetic conditions,” says Scheinman. “Our program and its experts will be a valuable resource for both patients and referring physicians.
Narrowing Vessels and Aneurysms
Because diseased blood vessels tend to re-narrow over time after vascular bypass surgery or other treatments, the long-term success of such procedures can be limited. The lab of Michael Conte, MD, chief of the Division of Vascular and Endovascular Surgery, is working to address this concern. “Our goals are to develop new drug and molecular therapies to prevent failures of angioplasty, stents and bypass grafts due to vessel re-narrowing, and to better identify patients at increased risk,” says Conte.
UCSF vascular surgeons were the first to design, make and use bifurcated stent grafts for aneurysms of the abdominal aorta, an approach that has become the mainstay of aneurysm management worldwide. Aneurysms are bulges or ballooning in a blood vessel caused by weakening in the vessel wall, and a bifurcated stent graft uses a type of stent (a tubular device placed inside a blood vessel to bypass an obstruction) that is designed to be implanted in a two-branch vessel.
UCSF surgeons also were the first to use multibranched stent grafts to treat aneurysms of the thoracoabdominal aorta, resulting in rates of death and disability far lower than with conventional surgical repair of extensive aneurysms in this inaccessible portion of the aorta.
Kathleen Dracup, RN, DNSc, FNP, FAAN, dean emeritus, UCSF School of Nursing
Rong Wang, PhD, Mildred V. Strouss Endowed Chair in Vascular Surgery, studies the processes by which blood vessels are formed and develop into the body’s arteries and veins. These processes are critical to how the body adapts to blocked arteries, such as in peripheral artery disease, and may lead to new treatments for patients to avoid surgery. Her work has also led to new insights into abnormal blood vessel formations called arteriovenous malformations, which can cause stroke and disability.
Taking the Work Directly to Patients
Other UCSF investigators are conducting clinical and translational work to further benefit heart and vascular patients. The research includes:
- Stem cell therapy for heart attacks: Researchers at UCSF Medical Center were involved in early-stage clinical trials to evaluate the safety and effectiveness of an adult stem cell therapy for patients who have just had their first heart attack. As part of a multicenter, national study, the researchers hope that the use of stem cells will combat the symptoms that continue to develop following a heart attack. “The goal of our research program is to better understand the role of stem cells in treating the millions of patients with weakened heart muscle and heart failure,” says Yerem Yeghiazarians, MD, co-director of the Cardiac Catheterization Laboratory, director of the UCSF Translational Cardiac Stem Cell Program and lead investigator of the cardiac stem cell study.
- Safer, less invasive repair of damaged heart valves: Cardiothoracic surgeon Elaine Tseng, MD, conducts research with engineers and vascular surgeons to improve surgical procedures for damaged heart valves through the use of less invasive devices. These procedures use a catheter (a small tube that can be laced through a patient’s circulatory system) to place a stent graft containing valve leaflets (tubular devices with a valve inside placed inside a blood vessel to relieve valve obstruction). This approach does not require a large incision and has a shorter recovery time than open surgery. Through research in the Cardiac Biomechanics Laboratory, the team has invented a transcatheter valve for surgical valves that have failed.
- Helping rural patients manage their heart disease: Kathleen Dracup, RN, DNSc, professor and immediate past dean of the UCSF School of Nursing, is world-renowned for her work with heart disease patients and their families. In one of her most recent research projects, she co-leads a multistate study looking at ways to better monitor fluid levels in heart failure patients in rural areas. Prior studies in urban settings, where patients are closer to care, have shown that this type of careful monitoring and patient education can reduce hospital readmissions.
- Improved monitoring and diagnoses: Another nursing school researcher, Barbara Drew, RN, PhD, develops and tests new monitoring strategies and improves clinical practices for more accurate diagnoses of arrhythmias and myocardial ischemia, a condition in which the blood flow to the heart is impaired.