Search

Unlabelled: Previously, we reported a missense mutation (C722G) in the M2-muscarinic acetylcholine receptor (CHRM2) gene associated with familial dilated cardiomyopathy. However, the exact molecular mechanisms by the related protein changes of CHRM2-C722G mutation induced are still unclear. CHRM2 and CHRM2-C722G lentiviral vector was infected to CHO cells. Proteomic analysis by label-free shotgun strategy and the STRING 9.0 software were performed. A total of 102 proteins with at least 2-fold change in the CHRM2-C722G group were identified, 42 proteins were up-regulated, whereas 57 were down-regulated. These altered proteins belong to three broad functional categories: (i) metabolic (e.g. Cytosolic acyl coenzyme A thioester hydrolase, Malate dehydrogenase); (ii) cytoskeletal (e.g. Actin-related protein, Myosin light polypeptide 6 and Alpha-actinin-1) and (iii) stress response (e.g. heat shock protein 70, Ras-related protein Rab-10). Interestingly, the marked differences in the expression of selected eight proteins (change >4.0-fold), were connected with many proteins related to apoptosis and immune/inflammatory response such as: FOS, BAX, MYC, TP53 and IL6. This novel study demonstrated for the first time a full-scale screening of the proteomics research by CHRM2-C722G mutation and profiled 102 changed proteins, of which, eight might be critical in cardiac dysfunction for future mapping., Significance: It was a full-scale screening of the proteomics research by CHRM2-C722G mutation. These proteins might serve as valuable biomarkers that could predict the presence of a precursor field. These proteins might serve to further explore the pathophysiological mechanisms in familial DCM patients with C176W mutation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: β1-adrenoceptors (β1-ARs) are the predominant receptors in regulating heart functions. β1-ARs contain 7-transmembrane domains (7TM), 3 extracellular loops and 3 intracellular loops. Among these loops, the second extracellular loop of β1-AR (β1-AR-ECII) plays an important role in the pathogenesis of heart failure., Methods: (1) Select the sera-negative rats for antibodies against β1-AR-ECII. (2) Detect the level of antibodies against β1-AR-ECII in the process of active immunization with artificial synthetic peptides according to the sequence of human β1-AR-ECII. (3) Observe its long-term role on cardiac structure and function in vivo by immunizing rats. (4) Detect the changes of T lymphocytes subsets in the process of active immunization., Results: The peptides induced the production of specific autoantibody against β1-AR-ECII. Furthermore, immunization with β1-AR-ECII peptide induced both morphological and functional alterations in the hearts of rats, which potentially results in heart failure. In addition, induction of the autoantibodies against β1-AR-ECII increased the CD4+/CD8+ ratio in the peripheral blood of rats., Discussion: In this study, we determined the effect of anti-β1-AR-ECII autoantibody on morphological and functional cardiomyopathic alterations by immunization of rats with a synthetic peptide corresponding to the β1-AR-ECII for 18 months. These results provide further evidence that autoantibody against β1-AR-ECII is involved in the pathogenesis of heart failure. But the underlying mechanisms need further study., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)