Altered myocardial expression of ghrelin and its receptor (GHSR-1a) in patients with severe heart failure.
Ghrelin is a peptide hormone mainly produced by the stomach, which strongly stimulates the release of growth hormone (GH) via the GH secretagogue receptor 1a (GHSR-1a) located in the hypothalamus. It has been reported to exert performance-enhancing effects on myocardial function, and as both ghrelin and GHSR-1a are expressed in myocardial tissues, the ghrelin system may have a direct GH-independent impact on cardiac function. We intended to investigate the expression of ghrelin and its receptor GHSR-1a in different myocardial areas of patients with chronic heart failure (CHF) as compared to heart-healthy subjects to better define the role of the ghrelin signaling system in the networks regulating cardiac function and its potential as a target for diagnosis and/or treatment of CHF. Myocardium biopsies of 12 patients undergoing heart transplantation and suffering from CHF were obtained. Expression of both ghrelin and GHSR-1a was assessed by means of immunohistochemistry and real-time PCR. Expression of ghrelin was significantly decreased in CHF hearts both in atrium and ventricles in comparison to the control hearts (p<0.05). The expression of the GHS-1a receptor was significantly increased in the CHF biopsies as compared to controls (p<0.05). No significant differences were found between the anatomical areas studied. Expression of myocardial ghrelin and GHSR-1a is directly associated with myocardial function: CHF hearts exhibit an impaired ghrelin production which might reflect maladaptive processes and an - probably compensatory - increase in GHSR-1a expression. These findings may open up new perspectives regarding the potential of ghrelin signaling as a target for pharmacological modulation.
Beiras-Fernandez
Andres
A
Department of Cardiac Surgery, Ludwig-Maximilian-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. Andres.Beiras@med.uni-muenchen.de
Kreth
Simone
S
Weis
Florian
F
Ledderose
Carola
C
Pöttinger
Thomas
T
Dieguez
Carlos
C
Beiras
Andres
A
Reichart
Bruno
B
D000328:Adult; D054439:Ghrelin / Q000235:genetics / Q000378:metabolism*; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054439:Ghrelin; D054440:Receptors, Ghrelin