Published online before print April 2, 2007, doi: 10.1161/HYPERTENSIONAHA.107.089052
(Hypertension. 2007;49:1225.)
© 2007 American Heart Association, Inc.
Editorial Commentaries |
Linking Cardiac Mechanosensing at the Sarcomere M-Band, Nuclear Factor 
B Signaling, and Cardiac Remodeling
From the Franz-Volhard Clinic (M.W.B.), Department of Cardiology, HELIOS Klinikum-Berlin, Charite Campus Berlin-Buch and Campus Virchow, Berlin, Germany; and the Hubrecht Laboratory and Interuniversity Cardiology Institute Netherlands (L.J.D.W.), Royal Netherlands Academy of Sciences, Utrecht, the Netherlands.
Correspondence to Martin W. Bergmann, Franz Volhard Clinic, HELIOS Kliniken Berlin and Charité Campus Buch, Wiltbergstrasse 50, 13125 Berlin, Germany. E-mail martin.bergmann@charite.de
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
How the heart senses increased biomechanic stress and converts this "input signal" to generalized downstream cardiac hypertrophy signaling paradigms remains an enigmatic but intriguing question in modern cardiovascular biology. Only recently have signaling molecules that can couple biomechanical stress to common pathways of cardiac hypertrophy been uncovered. Yeast-2-hybrid screens have identified several binding partners of sarcomeric proteins. These concerted actions revealed that especially the sarcomere Z-disc harbors key components that affect the activity of several notable kinases and phosphatase, including mitogen-activated protein kinases, protein kinases A and C, and calcineurin.1 Exemplary to this is the family of calsarcin proteins, which link the Z-disk protein 
-actinin to calcineurin, a well-characterized Ca2+-responsive signaling molecule controlling activity of the transcription factor NFAT and both required and sufficient for cardiac hypertrophy after pleiotropic stimuli (Figure).2 However, interruption of the calcium overload typical for heart failure may not stop disease progression, and, therefore, Ca2+-independent signaling cascades might serve as useful targets to interfere with left ventricular (LV) remodeling on pressure overload or ischemia.3
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Likewise, the giant sarcomeric protein titin is the starting point of a signaling complex where the zinc-finger protein nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres. In turn, p62 interacts with MuRF2, a muscle-specific RING-B-box E3 ligase and ligand of the transactivation domain of the serum response transcription factor. Nuclear translocation of MuRF2, provoked by mechanical inactivity, causes reduction of
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