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Transforming growth factor beta signaling in adult cardiovascular diseases and repair
Authors:Thomas Doetschman  Joey V. Barnett  Raymond B. Runyan  Todd D. Camenisch  Ronald L. Heimark  Henk L. Granzier  Simon J. Conway  Mohamad Azhar
Affiliation:(1) BIO5 Institute, University of Arizona, Tucson, AZ 85724, USA;(2) Department of Cellular and Molecular Medicine, University of Arizona, 1656 E Mabel St, PO Box 245217, Tucson, AZ 85724, USA;(3) Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA;(4) Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85724, USA;(5) Steele Children’s Research Center, University of Arizona, Tucson, AZ 85724, USA;(6) Southwest Environmental Health Sciences Center, University of Arizona, Tucson, AZ 85724, USA;(7) Cancer Biology Graduate Interdisciplinary Program, and Department of Surgery, University of Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, AZ 85724, USA;(8) Molecular Cardiovascular Research Program, Sarver Heart Center, Department of Physiology, University of Arizona, Tucson, AZ 85724, USA;(9) Program in Developmental Biology and Neonatal Medicine, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
Abstract:The majority of children with congenital heart disease now live into adulthood due to the remarkable surgical and medical advances that have taken place over the past half century. Because of this, adults now represent the largest age group with adult cardiovascular diseases. It includes patients with heart diseases that were not detected or not treated during childhood, those whose defects were surgically corrected but now need revision due to maladaptive responses to the procedure, those with exercise problems and those with age-related degenerative diseases. Because adult cardiovascular diseases in this population are relatively new, they are not well understood. It is therefore necessary to understand the molecular and physiological pathways involved if we are to improve treatments. Since there is a developmental basis to adult cardiovascular disease, transforming growth factor beta (TGFβ) signaling pathways that are essential for proper cardiovascular development may also play critical roles in the homeostatic, repair and stress response processes involved in adult cardiovascular diseases. Consequently, we have chosen to summarize the current information on a subset of TGFβ ligand and receptor genes and related effector genes that, when dysregulated, are known to lead to cardiovascular diseases and adult cardiovascular deficiencies and/or pathologies. A better understanding of the TGFβ signaling network in cardiovascular disease and repair will impact genetic and physiologic investigations of cardiovascular diseases in elderly patients and lead to an improvement in clinical interventions.
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