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Proteomics highlights decrease of matricellular proteins in left ventricular assist device therapy†. | LitMetric

AI Article Synopsis

  • * Our study identified over 1,700 proteins, revealing a reduction in specific proteins related to inflammation and heart function after LVAD, while some proteins linked to metabolic processes increased.
  • * The results highlight notable variability between patients in terms of how LVAD therapy influences heart protein profiles, indicating that matricellular proteins and alpha-1-antichymotrypsin could serve as key markers for future research and treatment evaluation.

Article Abstract

Objectives: We investigated the impact of mechanical unloading with a left ventricular assist device (LVAD) on the myocardial proteome.

Methods: We collected 11 patient-matched samples of myocardial left ventricular tissue of patients with non-ischaemic dilate cardiomyopathy, harvested at time of LVAD implant ('pre-LVAD') and heart transplant ('post-LVAD'). Samples were studied by quantitative proteomics. Further we performed histological assessment of deposited collagens and immune infiltration in both pre- and post-LVAD samples.

Results: A core set of  >1700 proteins was identified and quantified at a false discovery rate  <1%. The previously established decrease post-LVAD of alpha-1-antichymotrypsin was corroborated. We noted a post-LVAD decrease of matricellular proteins and proteoglycans such as periostin and versican. Also, proteins of the complement system and precursors of cardiac peptide hormones were decreased post-LVAD. An increase post-LVAD was evident for individual proteins linked to the innate immune response, proteins involved in diverse metabolic pathways, and proteins involved in protein synthesis. Histological analysis did not reveal significant alterations post-LVAD of deposited collagens or immune infiltration. The proteomic data further highlighted a pronounced inter-patient heterogeneity with regards to the impact of LVAD therapy on the left ventricular myocardial proteome. Finally, the proteomic data showed differential proteolytic processing in response to LVAD therapy.

Conclusions: Our findings underline a strong impact of LVAD therapy on the left ventricular myocardial proteome. Together with previous studies, protein markers of LVAD therapy such as alpha-1-antichymotrypsin are becoming apparent. Further, matricellular proteins are emerging as important components in response to LVAD therapy.

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Source
http://dx.doi.org/10.1093/ejcts/ezx023DOI Listing

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