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(Circulation Research. 2006;98:294.)
© 2006 American Heart Association, Inc.

Editorials

GDF15, a Cardioprotective TGF-ß Superfamily Protein

Tetsuro Ago, Junichi Sadoshima

From the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, UMDNJ, New Jersey Medical School, Newark.

Correspondence to Junichi Sadoshima, Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, UMDNJ, New Jersey Medical School, 185 South Orange Avenue, MSB G-609, Newark, NJ 07103. E-mail sadoshju@umdnj.edu

See related articles, pages 342–350 and 351–360

Key Words: GDF15 • TGF-ß superfamily • Smad • MAPK • hypertrophy • heart failure

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
The transforming growth factor-ß (TGF-ß) superfamily proteins, comprising more than 40 members (broadly divided into the TGF-ßs/activins/nodal family and the bone morphogenetic proteins [BMPs]/Müllerrian inhibiting substance/growth and differentiation factors [GDFs] family), were originally identified as molecules important for regulating development, differentiation, and tissue repair in various organs.¹ TGF-ß1, a founding member of the TGF-ß superfamily, plays a key role in mediating cardiac hypertrophy² and remodeling after myocardial infarction (MI) as an autocrine/paracrine factor.³ Increased TGF-ß1 expression is considered one of the few molecular markers that potentially discriminate between compensated and decompensated cardiac hypertrophy.³ Although TGF-ß1 may function protectively after MI by promoting scar formation, inhibiting neutrophil infiltration, and facilitating cardiomyogenic differentiation of adult hematopoietic stem cells,⁴ such beneficial effects last only briefly and sustained activation of TGF-ß1 causes structural remodeling, eventually leading to cardiac failure.⁵ Thus, TGF-ß1 is generally regarded as detrimental, inducing cardiac hypertrophy and failure in the adult heart.

Compared with the wealth of knowledge regarding the effects of TGF-ß1 on the heart, much less is known as to how other members of the TGF-ß superfamily affect cardiac hypertrophy and failure.⁶ In this issue of Circulation Research, two companion articles report the effect of growth and differentiation factor 15 (GDF15), a 12-kDa secreted protein (and a 25-kDa disulfide-linked dimer) belonging to the TGF-ß superfamily, on cardiac hypertrophy and apoptosis.^7,8 GDF15 is highly expressed in the placenta and the prostate, but not normally in many other organs, including the heart.^9,10 However, expression of GDF15 is induced rapidly by . . . [Full Text of this Article]

Related Article:

GDF15/MIC-1 Functions As a Protective and Antihypertrophic Factor Released From the Myocardium in Association With SMAD Protein Activation

Jian Xu, Thomas R. Kimball, John N. Lorenz, David A. Brown, Asne R. Bauskin, Raisa Klevitsky, Timothy E. Hewett, Samuel N. Breit, and Jeffery D. Molkentin
Circ. Res. 2006 98: 342-350. [Abstract] [Full Text] [PDF]