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CLINICAL RESEARCH: HEART FAILURE

Myotrophin in human heart failure

^* Department of Medicine and Therapeutics, University of Leicester, Leicester Royal Infirmary, Leicester, United Kingdom

Manuscript received November 27, 2002; revised manuscript received January 6, 2003, accepted January 24, 2003.

^* Reprint requests and correspondence: Dr. Leong L. Ng, Department of Medicine and Therapeutics, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom.
lln1{at}le.ac.uk

OBJECTIVES: The goal of this study was to investigate plasma levels of myotrophin in heart failure (HF) and their relationship to gender and disease severity.

BACKGROUND: Myotrophin is a myocardial hypertrophy-inducing factor initially demonstrated in hypertrophied and cardiomyopathic hearts. Recent evidence suggests an interaction with the transcription factor nuclear factor kappa B (NFB), which is activated in HF and modulates myocardial protein expression. It is unknown whether this peptide has an endocrine/paracrine role in man. We hypothesized that it may have a role in HF and would be raised in plasma.

METHODS: We developed a competitive binding assay specific for human myotrophin. Myotrophin was measured in plasma extracts of 120 HF patients and 130 age- and gender-matched normal controls.

RESULTS: Myotrophin in plasma existed as the full-length 12 kD form with also a 2.7 kD form (possibly a degradation product). Log normalized myotrophin levels were significantly elevated in HF patients (mean ± SEM [geometric mean, range], 2.402 ± 0.021 [252, 72 to 933] vs. 2.268 ± 0.021 [185, 28 to 501] fmol/ml, p < 0.0005). There was no relationship between myotrophin and age or gender in controls. However, males with HF had higher levels of myotrophin than females (p < 0.001). There was an inverse relationship of myotrophin levels with New York Heart Association class in patients with no gender difference in the relationship.

CONCLUSIONS: There is evidence of early activation of the myotrophin system in HF, which is more evident in males. This response is attenuated in more severe disease. The contribution of myotrophin to NFB-mediated gene transcription and preservation of cardiac muscle mass remains to be investigated further.

Abbreviations and Acronyms   HF   heart failure   ILMA   immunoluminometric assay   LV   left ventricle/ventricular   mRNA   messenger ribonucleic acid   NFB   nuclear factor kappa B   NYHA   New York Heart Association   streptavidin-MAE   streptavidin labeled with methyl-acridinium ester   TNF   tumor necrosis factor-alpha

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