Background Hypoxia is a common feature of many congenital heart defects (CHDs) and significantly contributes to their pathophysiology. Thus, understanding the mechanism underlying cell response to hypoxia is vital for the development of novel therapeutic strategies. Certainly, the hypoxia inducible factor (HIF) has been extensively investigated and it is now recognized as the master regulator of cell defense machinery counteracting hypoxic stress. Along this line, we recently discovered and reported a novel mechanism of HIF activation, which is mediated by sialidase NEU3. Thus, aim of this study was to test whether NEU3 played any role in the cardiac cell response to chronic hypoxia in congenital cyanotic patients. Methods Right atrial appendage biopsies were obtained from pediatric patients with cyanotic/non-cyanotic CHDs and processed to obtain mRNA and proteins. Real-Time PCR and Western Blot were performed to analyze HIF-1Î± and its downstream targets expression, NEU3 expression, and the NEU3 mediated effects on the EGFR signaling cascade. Results Cyanotic patients showed increased levels of HIF-1Î±, NEU3, EGFR and their downstream targets, as compared to acyanotic controls. The same patients were also characterized by increased phosphorylation of the EGFR signaling cascade proteins. Moreover, we found that HIF-1Î± expression levels positively correlated with those recorded for NEU3 in both cyanotic and control patients. Conclusions Sialidase NEU3 plays a central role in activating cell response to chronic hypoxia inducing the up-regulation of HIF-1Î±, and this represent a possible novel tool to treat several CHD pathologies.
NEU3 sialidase role in activating HIF-1Î± in response to chronic hypoxia in cyanotic congenital heart patients / M. Piccoli, E. Conforti, A. Varrica, A. Ghiroldi, F. Cirillo, G. Resmini, F. Pluchinotta, G. Tettamanti, A. Giamberti, A. Frigiola, L. Anastasia. - In: INTERNATIONAL JOURNAL OF CARDIOLOGY. - ISSN 0167-5273. - 230(2017 Mar), pp. 6-13.
|Titolo:||NEU3 sialidase role in activating HIF-1Î± in response to chronic hypoxia in cyanotic congenital heart patients|
ANASTASIA, LUIGI (Ultimo) (Corresponding)
|Parole Chiave:||chronic hypoxia; congenital heart defects; EGFR signaling pathway; HIF-1Î±; sialidase NEU3; Medicine (all); cardiology and cardiovascular medicine|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||mar-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.ijcard.2016.12.123|
|Appare nelle tipologie:||01 - Articolo su periodico|