Abstract

 
 
 
 Purpose: To investigate the effect of C-X-C motif chemokine receptor 2 (CXCR2) and cytoplasmic polyadenylation element binding protein 1 (CPEB1) which are linked to inflammatory and cellular senescence, on cardiac cachexia.
 Methods: Early and advanced stages of cardiac cachexia were established in mice using exogenous injection of single doses of growth differentiation factor 11 (GDF11, 3.0 and 6.0 mg/kg, respectively). The expressions of CXCR2 and CPEB1 were assayed using immonohistochemistry and Western blotting.
 Results: Following two weeks of GDF11 injection, cardiac tissue mass was reduced by 23 and 39 % in early and advanced stages cardiac cachexia, respectively, in mice. Histology showed progressive loss of cardiac muscle and cardiomyocyte shrinkage in early stage, with extensive cardiac muscle wasting and disruption of cardiac arche structure in the advanced stage. Immunohistochemistry and Western blotting showed that CXCR2 was 4.6 times overexpressed in the initial stage of cachexia, but was restricted to only 2.4-fold overexpression in advanced stage of cardiac cachexia. The results showed that CXCR2 and its higher expression in early stages of cardiac cachexia prepared the cardiac microenvironment for vast changes during which its expression was limited. There were 2.2-fold and 5.5-fold higher expressions of CPEB1 in early and advanced stages of cardiac cachexia, respectively, indicating its role in cardiac muscle wasting and remodelling in cellular senescence.
 Conclusion: CXCR2 overexpression modulates extensive cardiac muscle loss in cardiac cachexia, thus affording a strategy for the management of this pathological condition.
 
 
 
Highlights
Cardiac cachexia is a condition of muscle loss due to chronic inflammation, insulin resistance and functional incapability as a result of elevated neurohormonal activation [1]
In the mice injected with 3.0 mg/kg of growth differentiation factor 11 (GDF11), the cardiac weight was reduced by 23 % following 14 days of incubation, implying cardiac muscle loss
The dissected heart tissues from initial and advanced stages of cardiac cachexia mice were compared with heart tissue from control mice
Summary
Cardiac cachexia is a condition of muscle loss due to chronic inflammation, insulin resistance and functional incapability as a result of elevated neurohormonal activation [1]. In 2014, Europe alone had 1.2 million individual cardiac cachexia cases, with a mortality of over 20 - 40 % [3]. Recent advances have been made in understanding the mechanisms involved in the etiology of cardiac cachexia, translating them to achieve clinical success is still a challenge. There is no therapy or treatment for preventing or suppressing cardiac cachexia. Studies in this aspect are needed to evolve more effective ways of reversing cardiac cachexia, instead of treating the symptoms alone
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