Texas Heart Institute study reveals genes critical to heart repair after cardiac injury
Researchers in Cardiomyocyte Renewal Lab pave the way for new discovery
Houston, TX (June 7, 2016) – The Texas Heart Institute Cardiomyocyte Renewal Laboratory published study results in Nature that reveal expression of Pitx2 is induced in injured adult hearts when the Hippo pathway is removed, as well as in injured young hearts, promoting heart repair following myocardial infarction. This genetic discovery – made by James F. Martin, MD, PhD and his colleagues – unveils new insights critical to better understanding components of genetic pathways that enable cardiomyocyte self-renewal for cardiac repair.
Following the discovery of the genetic Hippo pathway and the ability of the heart to regenerate in Hippo-deficient models, Martin’s lab sought to unveil the specific factors that promote this renewal. An established Hippo-deficient heart regeneration mouse model was used to identify Pitx2, the cardiomyocyte-specific gain-of-function of which efficiently protected the hearts after cardiac injury. Genomic analyses indicated that genes encoding electron transport chain components and scavengers of reactive oxygen species were activated by Pitx2, whereas Pitx2-deficient neonatal mouse hearts failed to repair. “The significance in discovering that there are genes induced upon injury that are adaptive and help the heart respond to the injury and encourage repair is far-reaching,” said Martin, Director of the Cardiomyocyte Renewal Laboratory. “While there’s still much to learn, this puts us on an inside track to uncover ways to manipulate these genes and ultimately improve our ability to repair damaged hearts.”
These latest results from Dr. Martin’s study build upon his lab’s portfolio of work – focused on understanding how specialized signaling pathways are connected to adult tissue development and regeneration – which began at Texas Heart Institute in 2011. “This is very important work from Dr. Martin’s laboratory that continues to elucidate the importance of the Hippo pathway and its manipulation in promoting regeneration of the heart following injury in murine models,” said James Willerson, MD, President of Texas Heart Institute. “The demonstration that Pitx2 plays a role in the regeneration of Hippo-deficient hearts following myocardial injury is a new insight that almost certainly will provide alternative means for cardiac regeneration. We are very proud of Dr. Martin and his work, all of which is very much in support of the Texas Heart Institute’s strong desire to develop biologic interventions that promote the regeneration of heart muscle cells following injuries, such as a heart attack.”
The Cardiomyocyte Renewal Laboratory is dedicated to identifying new therapeutic options to promote normal regenerative capabilities in the heart and prevent disorders such as heart failure and atrial fibrillation.
About the Texas Heart Institute
The Texas Heart Institute, founded by world-renowned cardiovascular surgeon Dr. Denton A. Cooley in 1962, is a nonprofit organization dedicated to reducing the devastating toll of cardiovascular disease through innovative and progressive programs in research, education and improved patient care.
Tao G, Kahr PC, Morikawa Y, Zhang M, Rahmani M, Heallen TR, Li L, Sun Z, Olson EN, Amendt BA and Martin JF.. “Pitx2 promotes heart repair by activating the antioxidant response after cardiac injury.” Nature. 2016;534(7605):119-23. Pubmed PMID: 27251288