Transforming growth factor beta signaling in adult cardiovascular diseases and repair

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, the adults now represent the largest age group with adult cardiovascular diseases. They include 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.

Histone Deacetylase 3 Coordinates Deacetylase-independent Epigenetic Silencing of Transforming Growth Factor-β1 (TGF-β1) to Orchestrate Second Heart Field Development

“…Our data establish that loss of HDAC3 triggers EndMT in the outflow tract cushion that can be markedly reduced by inhibiting TGF-␤. Indeed, TGF-␤ and its downstream target genes are critical regulators of EndMT (17). In particular, TGF-␤-activated SMAD proteins directly stimulate the expression of zinc finger transcription factor Snai1 within the outflow tract cushion (40).…”

TGF-β in aging and disease

“…The TGF-β signaling network in cardiovascular damage and repair is the topic of the review by Doetschman et al (2011). The majority of children with congenital heart disease now live into adulthood because of remarkable surgical and medical advances.…”

TGFβ Signaling and Cardiovascular Diseases

“…Likewise studies in human further corroborated the importance of TGF signaling in vascular function. Mutations in TGF family genes or mutations, which lead to missregulated TGF signaling result in vascular pathologies, such as arteriovenous malformations (AVMs), aneurysms, hypertension, atherosclerosis and cardiovascular disease [3,4,7]. Cardiovascular disease is by far the largest chronic health problem causing significant morbidity, mortality and despite the advances in preventive and therapeutic strategies, it remains the leading cause of death worldwide.…”