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(Circulation. 2000;101:2674.)
© 2000 American Heart Association, Inc.
Brief Rapid Communications |
Decreased Expression of the Cardiac LIM Domain Protein MLP in Chronic Human Heart Failure
From Klinik III für Innere Medizin, Universität zu Köln, Köln, Germany (O.Z., M.B.), and Friedrich Miescher Institute, Basel, Switzerland (P.C.).
Correspondence to Prof Dr Michael Böhm, Klinik III für Innere Medizin, Joseph-Stelzmann-Str 9, 50924 Köln, Germany. E-mail michael.boehm{at}medizin.uni-koeln.de
Background—The cardiac LIM domain protein MLP, a member of the cysteine-rich protein family, is an essential regulator of cardiac muscle development. Mice with a disruption of the MLP gene resemble the morphological and clinical picture of dilated cardiomyopathy and heart failure in humans. We investigated whether altered MLP expression is significant for the pathogenesis of human heart failure.
Methods and Results—Immunohistochemistry and in situ
hybridization confirmed the expression of MLP protein and mRNA in human
cardiomyocytes. Western blot analysis revealed that
the MLP peptide was present in the contractile protein fraction but
not in the cytosolic or membrane fraction and that the binding of MLP
to myofibrils required functional zinc finger domains. MLP
immunoreactivity was decreased 
50% (P<0.05) in the
left ventricular myocardium of patients with
chronic heart failure due to dilated or ischemic
cardiomyopathy compared with non-failing donor
hearts. MLP mRNA expression, as assessed by Northern blot experiments,
was not significantly different between failing and non-failing control
hearts, which suggests that decreased MLP synthesis or increased MLP
protein turnover, rather than a decreased number of RNA transcripts,
may play a role.
Conclusions—Because MLP may promote myofibril assembly, the down-regulation of this adapter protein might play an essential role in myofibril derangement or impaired myofibril rearrangement in the failing human myocardium.
Key Words: heart failure • cardiomyopathy • genes • RNA
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