Novel proteins associated with human dilated cardiomyopathy: selective reduction in α_1A-adrenergic receptors and increased desensitization proteins

Abstract

Therapeutics to treat human heart failure (HF) and the identification of proteins associated with HF are still limited. We analyzed α₁-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 β-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 β₁-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 β₁-AR in HF, there is also a concomitant loss of α_1A-ARs, which are considered cardioprotective proteins.

• Adrenergic
• alpha1
• desensitization
• heart failure
• proteomics
• receptor

Acknowledgments

We would like to thank Life Banc of Northeast Ohio for the non-failing heart samples and the cardiac transplant teams at Cleveland Clinic.