Novel proteins associated with human dilated cardiomyopathy: selective reduction in α(1A)-adrenergic receptors and increased desensitization proteins.
J Recept Signal Transduct Res
; 33(2): 96-106, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23384050
ABSTRACT
Abstract Therapeutics to treat human heart failure (HF) and the identification of proteins associated with HF are still limited. We analyzed α(1)-adrenergic receptor (AR) subtypes in human HF and performed proteomic analysis on more uniform samples to identify novel proteins associated with human HF. Six failing hearts with end-stage dilated cardiomyopathy (DCM) and four non-failing heart controls were subjected to proteomic analysis. Out of 48 identified proteins, 26 proteins were redundant between samples. Ten of these 26 proteins were previously reported to be associated with HF. Of the newly identified proteins, we found several muscle proteins and mitochondrial/electron transport proteins, while novel were functionally similar to previous reports. However, we also found novel proteins involved in functional classes such as ß-oxidation and G-protein coupled receptor signaling and desensitization not previously associated with HF. We also performed radioligand-binding studies on the heart samples and not only confirmed a large loss of ß(1)-ARs in end-stage DCM, but also found a selective decrease in the α(1A)-AR subtype not previously reported. We have identified new proteins and functional categories associated with end-stage DCM. We also report that similar to the previously characterized loss of ß(1)-AR in HF, there is also a concomitant loss of α(1A)-ARs, which are considered cardioprotective proteins.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Dilatada
/
Receptores Adrenérgicos alfa 1
/
Proteoma
/
Insuficiência Cardíaca
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Recept Signal Transduct Res
Assunto da revista:
BIOQUIMICA
/
FISIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos