Connective tissue disorders and cardiovascular complications: the indomitable role of transforming growth factor-beta signaling.
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.
Division of Cardiothoracic Surgery, Medical University of South Carolina, Strom Thurmond Research Building, 114 Doughty Street, Suite 326, 250778, Charleston, SC, 29425, USA.
Jason B
JB
Wheeler
John S
JS
Ikonomidis
Jeffrey A
JA
Jones
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017545:Aortic Aneurysm, Thoracic / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D001021:Aortic Valve / Q000473:pathology / Q000601:surgery; D000082882:Bicuspid Aortic Valve Disease; D005786:Gene Expression Regulation; D006330:Heart Defects, Congenital / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006349:Heart Valve Diseases / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008382:Marfan Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009154:Mutation; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D051785:Smad Proteins / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics*
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D057134:Antibodies, Neutralizing; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta