Proteomics highlights decrease of matricellular proteins in left ventricular assist device therapy†.
OBJECTIVE
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.
Deparment of Cardiac Surgery, University Hospital Basel, Basel, Switzerland.
Jasmin Hasmik
JH
Shahinian
Institute for Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany.
Bettina
B
Mayer
Institute for Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany.
Stefan
S
Tholen
Institute of Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany.
Kerstin
K
Brehm
Institute for Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany.
Martin L
ML
Biniossek
Institute of Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany.
Hannah
H
Füllgraf
Institute of Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany.
Selina
S
Kiefer
Institute of Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany.
Ulrike
U
Heizmann
Institute of Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany.
Claudia
C
Heilmann
Deparment of Cardiac Surgery, University Hospital Basel, Basel, Switzerland.
Florian
F
Rüter
Deparment of Cardiac Surgery, University Hospital Basel, Basel, Switzerland.
Martin
M
Grapow
Deparment of Cardiac Surgery, University Hospital Basel, Basel, Switzerland.
Oliver Thomas
OT
Reuthebuch
Deparment of Cardiac Surgery, University Hospital Basel, Basel, Switzerland.
Friedrich
F
Eckstein
Department of Cardiovascular Surgery, Heart Centre Freiburg University, Freiburg, Germany.
Friedhelm
F
Beyersdorf
Institute for Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany.|BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany.
Oliver
O
Schilling
Department of Cardiovascular Surgery, Heart Centre Freiburg University, Freiburg, Germany.
Matthias
M
Siepe
D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism / Q000601:surgery; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D011506:Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods*
D011506:Proteins
Left ventricular assist device ; Matrisome ; Mechanical unloading ; Reverse remodelling