title: Analysis of molecular changes after autologous cell therapy in swine myocardial infarction tissue can reveal novel targets for future therapy.
abstract: Although several studies have demonstrated a functional recovery of infarcted myocardial tissue after cell therapy, little is known about the molecular mechanisms behind it. The aim of this study was to characterize the effect of cell therapy at the molecular level to screen for novel target candidates for future therapy of infarcted myocardial tissue. We used a swine acute myocardial infarction model evoked by transient occlusion of the circumflex coronary artery. Autologous bone marrow-derived mononuclear cells (BMMCs) or saline were injected intramyocardially or into the circumflex coronary artery. Samples for protein and RNA analysis were collected from the infarction area and healthy myocardium after a 3 week recovery period and analysed by two-dimensional gel electrophoresis (2DE) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Proteomic screening detected 13 protein spots which were altered after infarction but had been restored by BMMC treatment. The identification of seven proteins by mass spectrometry revealed that five proteins with decreased expression after infarction corresponded to mitochondrial proteins involved in energy metabolism. Their restored levels after BMMC treatment indicate their involvement in the recovery of heart function. In contrast, the elevated levels of α-crystallin B chain and cathepsin D after infarction suggest an involvement in the pathological mechanisms causing a decreased heart function. This study reveals that cell therapy with BMMCs after myocardial infarction causes restoration of several altered protein levels after 3 weeks and identifies potential marker proteins involved in the pathology of infarction.
authors.affiliation: Institute of Clinical Medicine, Department of Surgery and Clinical Research Center, Oulu University Hospital and University of Oulu, Finland; Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, Finland. siri.lehtonen@oulu.fi.
authors.forename: Siri T
authors.initials: ST
authors.lastname: Lehtonen
authors.forename: Jussi
authors.initials: J
authors.lastname: Mäkelä
authors.forename: Steffen
authors.initials: S
authors.lastname: Ohlmeier
authors.forename: Kari
authors.initials: K
authors.lastname: Ylitalo
authors.forename: Tatu
authors.initials: T
authors.lastname: Juvonen
authors.forename: Vesa
authors.initials: V
authors.lastname: Anttila
authors.forename: Petri
authors.initials: P
authors.lastname: Lehenkari
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D064987:Cell- and Tissue-Based Therapy; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D006334:Heart Function Tests; D006439:Hemodynamics / Q000235:genetics; D007273:Injections, Intramuscular; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D040901:Proteomics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013318:Stroke Volume / Q000235:genetics; D034421:Sus scrofa; D014182:Transplantation, Autologous