Abstract
Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic root dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-β) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-β signaling pathway, heritable connective tissue syndromes related to TGF-β receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system.
MeSH terms
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Adrenergic beta-Antagonists / therapeutic use
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Angiotensin II Type 1 Receptor Blockers / therapeutic use
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Antibodies, Neutralizing / pharmacology
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Aortic Aneurysm, Thoracic / drug therapy
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Aortic Aneurysm, Thoracic / genetics*
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Aortic Aneurysm, Thoracic / pathology
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Aortic Aneurysm, Thoracic / surgery
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Aortic Valve / pathology
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Aortic Valve / surgery
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Bicuspid Aortic Valve Disease
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Gene Expression Regulation
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Heart Defects, Congenital / drug therapy
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Heart Defects, Congenital / genetics*
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Heart Defects, Congenital / pathology
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Heart Defects, Congenital / surgery
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Heart Valve Diseases / drug therapy
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Heart Valve Diseases / genetics*
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Heart Valve Diseases / pathology
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Heart Valve Diseases / surgery
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Humans
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Loeys-Dietz Syndrome / drug therapy
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Loeys-Dietz Syndrome / genetics*
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Loeys-Dietz Syndrome / pathology
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Loeys-Dietz Syndrome / surgery
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Marfan Syndrome / drug therapy
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Marfan Syndrome / genetics*
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Marfan Syndrome / pathology
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Marfan Syndrome / surgery
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Mutation
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Receptors, Transforming Growth Factor beta / genetics
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Signal Transduction / genetics*
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Smad Proteins / genetics
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Transforming Growth Factor beta / antagonists & inhibitors
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Transforming Growth Factor beta / genetics*
Substances
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Adrenergic beta-Antagonists
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Angiotensin II Type 1 Receptor Blockers
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Antibodies, Neutralizing
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Receptors, Transforming Growth Factor beta
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Smad Proteins
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Transforming Growth Factor beta
Supplementary concepts
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Aortic Aneurysm, Familial Thoracic 1