Cardiac pathologies in relation to Smad-dependent pathways

Interact Cardiovasc Thorac Surg. 2010 Oct;11(4):455-60. doi: 10.1510/icvts.2010.234773. Epub 2010 Jul 22.

Abstract

The transforming growth factor-β (TGF-β) superfamily are of structurally related proteins that mediate developmental processes including cell growth, apoptosis, cellular homeostasis, tissue differentiation, morphogenesis, proliferation, and migration. Smads are intracellular signaling effectors that mediate intracellular signaling of the TGF-β superfamily. They have been implicated in a wide range of cardiac disorders, including cardiac failure, cardiac fibrosis, myocardial infarction, injury induced by angioplasty, and pulmonary artery hypertension. They also have a function to regulate cardiac structural development in embryos. By binding to types I and II of serine-threonine kinase receptors, bone morphogenetic protein 2 (BMP2) enables phosphorylation of Smad1 to form hetero-oligomeric complexes with Smad4, and modulate the transcription of the target genes after they are translocated into the nucleus. Appropriate interventions, such as Smad-responsive transcriptional promoter and antifibrotic angiotensin-converting enzyme inhibitors, can be helpful in reversing cardiac abnormalities. The aim of this article is to describe the current research results of Smad proteins in terms of cardiac disorders and development through transforming growth factor (TGF)-β pathways.

MeSH terms

  • Bone Morphogenetic Proteins / metabolism
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / physiopathology
  • Humans
  • Signal Transduction
  • Smad Proteins / metabolism*
  • Transforming Growth Factor beta / metabolism*

Substances

  • Bone Morphogenetic Proteins
  • Smad Proteins
  • Transforming Growth Factor beta