The Role of Growth Factors in Cardiovascular Development

Dear Colleagues,

We welcome review and original article contributions that increase our understanding of growth factor pathway regulation in cardiovascular development and disease. Multifunctional growth factors and cytokines such as transforming growth factor beta (TGFβ), fibroblast growth factor (FGF), and bone morphogenetic proteins (BMPs) are produced in most cardiac cell types during cardiovascular development and in adult cardiovascular tissues and regulated by integrins, extracellular matrix proteins (e.g., Fibrillins, Elastin, Fibulins, Collagens, LTBPs), matrix metalloproteinases (MMPs), noggin, follistatin, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS) and ADAMTS-like proteins. Downstream signaling occurs through phosphorylation (e.g., TAK, p38, ERK1/2 MAPK) and nuclear translocation of transcription factors (e.g., SMAD2/3 in conjunction with SMAD4. Other transcription factors, such as TBX5 and NKX2-5, activate Wnt and FGF signaling. Growth factors-regulated gene expression controls cell differentiation, cell growth, apoptosis, cell migration, and extracellular matrix production and remodeling during cardiovascular development and pathogenesis of cardiovascular disease. Genetic mutations in growth factors, transcription factors (e.g., TBX5, NOTCH1), ECM (e.g., FBN1, ELN), and ECM remodeling (e.g., ADAMTS) pathways genes cause congenital heart disease, bicuspid aortic valve, mitral valve disease, and aortic aneurysm and dissection in patients of connective tissue disorders (including Loeys-Dietz and Marfan syndrome, Fibrodysplasia ossificans progressiva, Geleophysic dysplasia). Increased TGFβ and BMP expression is associated with cardiomyopathy, mitral valve prolapse, and aortic aneurysm in Marfan syndrome. Increased TGFβ signaling is found in cardiac fibrosis, cardiac hypertrophy, myocardial infarction and heart failure, hypertension, atherosclerosis, arterial calcification, and thoracic and abdominal aortic aneurysms. Fibrillin 1, TBX5, and ADAMTSL2 mutations result in altered TGFβ or FGF signaling and cardiovascular disease. Thus, understanding the cell-specific role and molecular and biochemical mechanisms of growth factors and regulation of their activation will lead to safer and more effective therapy for cardiovascular disease. Consequently, we invite author contributions that advance our understanding of growth signaling and its regulatory mechanisms in cardiovascular development and cardiovascular disease. We suggest the following themes for this Special Issue:

• Growth factors in cardiovascular development;
• Growth factors in aortopathy: Thoracic and abdominal aneurysm, arterial calcification, atherosclerosis;
• Growth factors in bicuspid aortic valve, mitral valve disease, calcification, aortic stenosis, and congenital heart defects;
• Growth factors in cardiac hypertrophy, cardiac fibrosis, heart failure;
• Growth factors in hypertension and atherosclerosis;
• Growth factors signaling mechanism using in vitro cell and tissue culture models;
• Novel models of growth factor signaling and its regulatory transcriptional factors in the cardiovascular system;
• Growth factors-based therapies of cardiovascular disease and cardiotoxicity.

Dr. Mohamad Azhar
Dr. Timothy J. Mead
Dr. Irfan Kathiriya
Guest Editors

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• cardiac development
• single ventricle defects
• cardiovascular disease
• growth factor
• TGF-β
• extracellular matrix
• ADAMTS
• aortic aneurysm and dissection
• heart valve
• cardiac hypertrophy
• cardiac fibrosis
• transcription factor
• gene regulation
• congenital heart defect
• matrix metalloproteinase
• cell-cell signaling