Decreased expression of the cardiac LIM domain protein MLP in chronic human heart failure.
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.


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 approximately 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.
Zolk
O
O
Klinik III für Innere Medizin, Universität zu Köln, Germany.
Caroni
P
P
Böhm
M
M
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000503:physiopathology; D002908:Chronic Disease; D015536:Down-Regulation / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D060588:LIM Domain Proteins; D008875:Middle Aged; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D013347:Subcellular Fractions / Q000378:metabolism; D016335:Zinc Fingers / Q000502:physiology
D060588:LIM Domain Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C090114:cysteine and glycine-rich protein 3