Copyright © 2005, European Society of Cardiology
The complex pattern of SMAD signaling in the cardiovascular system
Physiologisches Institut, Justus-Liebig Universität Giessen, Aulweg 129, 35392 Gießen, Germany
* Corresponding author. Tel.: +49 641 9947246; fax: +49 641 9947219. Email address: Gerhild.Taimor{at}physiologie.med.uni-giessen.de jacqueline.heger{at}physiologie.med.uni-giessen.de
The SMAD (small mother against decapentaplegic) family comprises transcription factors that function as signal transducers of TGFβ (transforming growth factor) superfamily members. The number of studies showing expression, activation or involvement of both SMAD and TGFβ family members in cardiovascular diseases is constantly rising. In this context, the position of SMADs in the diseased heart is particularly interesting because, besides their well-known fibrotic effects, increasing evidence demonstrates direct action of SMADs on cardiomyocytes as well as on the vascular system. In these systems, SMAD proteins are described to have effects on heart development, cell proliferation, cell growth, and apoptosis. As will be discussed in this review, these different consequences of SMAD activation are dependent on different SMAD isoforms, interaction of SMAD with other transcription factors in the particular situation, and modulation of SMAD activity by various kinases. As a result of all these influences, it turns out that activation of SMAD by members of the BMP (bone morphogenetic protein) family, which is a subfamily of the TGFβ superfamily, is necessary for correct heart development. On the other hand, activation of SMADs by TGFβ family members results in fibrotic, apoptotic, and anti-hypertrophic processes that are related to a detrimental cardiac remodeling and progression to heart failure.
KEYWORDS Transcription factors; TGFβ; BMP; Hypertrophy; Apoptosis
* Sian E. Harding acted as guest editor for this manuscript.
Time for primary review 33 days
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