A team of researchers from Texas Heart Institute, Texas Children’s Hospital and Baylor College of Medicine has uncovered new insights into the mechanisms underlying the progression of congenital heart disease (CHD) – a range of heart defects that develop before birth and remain the leading cause of child death.
Research published in Nature represents the first reported single-cell genomics evidence of unique differences in heart muscle cells and the immune system of patients with coronary artery disease. Uncovering these key differences and the progression of these diseases provides researchers with an opening to design new ways to treat coronary artery disease.
While the eventual outcome of heart failure in coronary artery disease is well documented, the underlying cause of the decline in heart function in these patients is still poorly understood. This lack of knowledge in understanding has led to obstacles in the development of new therapies capable of prolonging a patient’s life.
To answer these unanswered questions, James F. Martin, MD, PhD, of the Texas Heart Institute and Baylor College of Medicine, collaborated with Iki Adachi, MD, director of the Mechanical Circulatory Support Program at Texas Children’s and associate professor at Baylor College of Medicine, and Diwakar Turaga, MD, PhD, pediatric cardiac intensive care specialist at Texas Children’s Hospital and assistant professor at Baylor College of Medicine, to profile heart and blood samples from coronary patients. The team studied patients with hypoplastic left heart syndrome (HLHS), tetralogy of Fallot (TOF), and dilated (DCM) and hypertrophic (HCM) cardiomyopathies undergoing heart surgery.
Dr. Martin is an internationally renowned physician-scientist who has made many seminal contributions to our understanding of heart developmental pathways and disease, as well as tissue regeneration.
“Using several exciting new technologies such as single-cell RNA sequencing, we were able to interrogate CHD patient samples at the single-cell level. One of our goals is to improve the natural history of this terrible disease that afflicts children,” said Dr. Martin, Director of the Cardiomyocyte Renewal Laboratory at the Texas Heart Institute and Professor Vivian L. Smith in the Department of Physiology. integrative from Baylor College of Medicine. “Much work remains to be done as the team, including co-first authors Drs. Matthew C. Hill, Zachary A. Kadow and Hali Long, work towards this goal.”
Dr. Turaga is a physician-scientist dedicated to bringing cardiac regenerative medicine therapies to the bedside.
“This is the first step in the development of a comprehensive cell atlas of congenital heart disease,” said Dr. Turaga, a physician in the Texas Children’s Cardiac Intensive Care Unit, as well as an expert in genomics and microscopy. “We are creating a roadmap for therapies targeting individual cell types and unique genetic pathways in coronary artery disease that include both the heart and the immune system, which has not been reported before. As the technology matures, this will become the standard of care in treatment. of CHD.”
Dr. Adachi is a congenital heart surgeon at Texas Children’s Hospital who specializes in reconstructive surgical procedures for coronary lesions, including those analyzed in this study.
“What we’ve achieved with this study is absolutely exciting, but only the beginning,” said Dr. Adachi, director of the world’s largest pediatric heart transplant and ventricular assist device program. “The collaboration between the extremely sophisticated laboratory at the Texas Heart Institute and the top pediatric cardiac center at Texas Children’s certainly has the potential to go further.”
The study results not only provide a new roadmap for developing personalized treatments for coronary artery disease, but also provide the scientific community with an essential resource of rare pediatric cardiac samples that can be used to make new discoveries and dig deeper. our understanding of coronary artery disease.
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