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Potential regulatory effects of CXCR2 and CPEB1 on cardiac cachexia


Yang Li
Congyu Zhang
Qian Tong
Xiaoxing Feng

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.






Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996