title: Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function after severe myocardial injury.
abstract: BACKGROUND
  Apelin-13 (A13) regulates cardiac homeostasis. However, the effects and mechanism of A13 infusion after an acute myocardial injury (AMI) have not been elucidated. This study assesses the restorative effects and mechanism of A13 on the peri-infarct region in murine AMI model.
  
  
  METHODS
  51 FVB/N mice (12weeks, 30g) underwent AMI. A week following injury, continuous micro-pump infusion of A13 (0.5μg/g/day) and saline was initiated for 4-week duration. Dual contrast MRI was conducted on weeks 1, 2, 3, and 5, consisting of delayed-enhanced and manganese-enhanced MRI. Four mice in each group were followed for an extended period of 4weeks without further infusion and underwent MRI scans on weeks 7 and 9.
  
  
  RESULTS
  A13 infusion demonstrated preserved LVEF compared to saline from weeks 1 to 4 (21.9±3.2% to 23.1±1.7%* vs. 23.5±1.7% to 16.9±2.8%, *p=0.02), which persisted up to 9weeks post-MI (+1.4%* vs. -9.4%, *p=0.03). Mechanistically, dual contrast MRI demonstrated significant decrease in the peri-infarct and scar % volume in A13 group from weeks 1 to 4 (15.1 to 7.4% and 34.3 to 25.1%, p=0.02, respectively). This was corroborated by significant increase in 5-ethynyl-2'-deoxyuridine (EdU(+)) cells by A13 vs. saline groups in the peri-infarct region (16.5±3.1% vs. 8.1±1.6%; p=0.04), suggesting active cell mitosis. Finally, significantly enhanced mobilization of CD34(+) cells in the peripheral blood and up-regulation of APJ, fibrotic, and apoptotic genes in the peri-infarct region were found.
  
  
  CONCLUSIONS
  A13 preserves cardiac performance by salvaging the peri-infarct region and may contribute to permanent restoration of the severely injured myocardium.
authors: Department of Cardiovascular Medicine, Stanford University, Stanford, CA, USA; Department of Cardiovascular Medicine, Gachon University, Incheon, Republic of Korea; Gachon Cardiovascular Research Institute, Gachon University, Incheon, Republic of Korea.
authors: Wook-Jin
authors: WJ
authors: Chung
authors: Department of Pathology, Stanford University, Stanford, CA, USA.
authors: Ahryon
authors: A
authors: Cho
authors: Gachon Cardiovascular Research Institute, Gachon University, Incheon, Republic of Korea; Department of Anatomy and Cell Biology, Gachon University, Incheon, Republic of Korea; Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
authors: Kyunghee
authors: K
authors: Byun
authors: Gachon Cardiovascular Research Institute, Gachon University, Incheon, Republic of Korea; Center for Genomics and Proteomics & Stem Cell Core Facility, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.
authors: Jeongsik
authors: J
authors: Moon
authors: Department of Cardiovascular Medicine, Stanford University, Stanford, CA, USA.
authors: Xiaohu
authors: X
authors: Ge
authors: Division of Cardiology, Soon Chun Hyang University College of Medicine, Bucheon, Republic of Korea.
authors: Hye-Sun
authors: HS
authors: Seo
authors: Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
authors: Ejung
authors: E
authors: Moon
authors: Department of Cardiovascular Medicine, Stanford University, Stanford, CA, USA.
authors: Rajesh
authors: R
authors: Dash
authors: Department of Cardiovascular Medicine, Stanford University, Stanford, CA, USA. Electronic address: phillip@stanford.edu.
authors: Phillip C
authors: PC
authors: Yang
mesh_terms: D000818:Animals; D007262:Infusions, Intravenous; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000503:physiopathology; D016879:Salvage Therapy / Q000379:methods*; D012720:Severity of Illness Index; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C495199:apelin-13 peptide
keywords: Apelin-13; Magnetic resonance imaging; Myocardial infarction; Salvage; Stem cell