Proteomic analysis reveals significant elevation of heat shock protein 70 in patients with chronic heart failure due to arrhythmogenic right ventricular cardiomyopathy.
As proteins are the ultimate biological determinants of phenotype of disease, we screened altered proteins associated with heart failure due to arrhythmogenic right ventricular cardiomyopathy (ARVC) to identify biomarkers potential for rapid diagnosis of heart failure. By 2-dimensional gel electrophoresis and mass spectrometry, we identified five commonly altered proteins with more than 1.5 fold changes in eight ARVC failing hearts using eight non-failing hearts as reference. Noticeably, one of the altered proteins, heat shock protein 70 (HSP70), was increased by 1.64 fold in ARVC failing hearts compared with non-failing hearts. The increase of cardiac HSP70 was further validated by Western blot, immunochemistry, and enzyme-linked immunosorbent assay (ELISA) in failing hearts due to not only ARVC, but also dilated (DCM, n = 18) and ischemic cardiomyopathy (ICM, n = 8). Serum HSP70 was also observed to be significantly increased in heart failure patients derived from the three forms of cardiomyopathies. In addition, we observed hypoxia/serum depletion stimulation induced significantly elevation of intracellular and extracellular HSP70 in cultured neonatal rat cardiomyocytes. For the first time to our knowledge, we revealed and clearly demonstrated significant up-regulation of cardiac and serum HSP70 in ARVC heart failure patients. Our results indicate that elevated HSP70 is the common feature of heart failure due to ARVC, DCM, and ICM, which suggests that HSP70 may be used as a biomarker for the presence of heart failure due to cardiomyopathies of different etiologies and may hold diagnostic/prognostic potential in clinical practice.
Wei
Ying-Jie
YJ
Chinese Academy of Medical Sciences, Peking Union Medical College, Fuwai Hospital & Cardiovascular Institute, Key Laboratory of Cardiovascular Regenerative Medicine, Ministry of Health, Beijing, 100037, People's Republic of China. weiyingjiefw@126.com
Huang
Yin-Xia
YX
Shen
Ya
Y
Cui
Chuan-Jue
CJ
Zhang
Xiao-Ling
XL
Zhang
Hao
H
Hu
Sheng-Shou
SS
D000818:Animals; D000831:Animals, Newborn; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000150:complications* / Q000378:metabolism*; D015415:Biomarkers; D015153:Blotting, Western; D002478:Cells, Cultured; D015331:Cohort Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D032383:Myocytes, Cardiac / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D020543:Proteome