title: A Novel Collagen Matricryptin Reduces Left Ventricular Dilation Post-Myocardial Infarction by Promoting Scar Formation and Angiogenesis.
abstract: BACKGROUND
  Proteolytically released extracellular matrix (ECM) fragments, matricryptins, are biologically active and play important roles in wound healing. Following myocardial infarction (MI), collagen I, a major component of cardiac ECM, is cleaved by matrix metalloproteinases (MMPs).
  
  
  OBJECTIVE
  This study identified novel collagen-derived matricryptins generated post-MI that mediate remodeling of the left ventricle (LV).
  
  
  METHODS
  Recombinant collagen Ia1 was used in MMPs cleavage assays, the products were analyzed by mass spectrometry for identification of cleavage sites. C57BL6/J mice were given MI and animals were treated either with vehicle control or p1158/59 matricryptin. Seven days post-MI, LV function and parameters of LV remodeling were measured. Levels of p1158/59 were also measured in plasma of MI patients and healthy controls.
  
  
  RESULTS
  In situ, MMP-2 and -9 generate a collagen Iα1 C-1158/59 fragment, and MMP-9 can further degrade it. The C-1158/59 fragment was identified post-MI, both in human plasma and mouse LV, at levels that inversely correlated to MMP-9 levels. We synthesized a peptide beginning at the cleavage site (p1158/59, amino acids 1159 to 1173) to investigate its biological functions. In vitro, p1158/59 stimulated fibroblast wound healing and robustly promoted angiogenesis. In vivo, early post-MI treatment with p1158/59 reduced LV dilation at day 7 post-MI by preserving LV structure (p < 0.05 vs. control). The p1158/59 stimulated both in vitro and in vivo wound healing by enhancing basement membrane proteins, granulation tissue components, and angiogenic factors.
  
  
  CONCLUSIONS
  Collagen Iα1 matricryptin p1158/59 facilitates LV remodeling post-MI by regulating scar formation through targeted ECM generation and stimulation of angiogenesis.
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas; Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, Mississippi.
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Rugmani Padmanabhan
authors.initials: RP
authors.lastname: Iyer
authors.affiliation: San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Zamilpa
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Andriy
authors.initials: A
authors.lastname: Yabluchanskiy
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Kristine Y
authors.initials: KY
authors.lastname: DeLeon-Pennell
authors.affiliation: Division of Cardiology and Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Hall
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kaplan
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Fouad A
authors.initials: FA
authors.lastname: Zouein
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Dustin
authors.initials: D
authors.lastname: Bratton
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Flynn
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Presley L
authors.initials: PL
authors.lastname: Cannon
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas; Department of Electrical and Computer Engineering, University of Texas at San Antonio, San Antonio, Texas.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Jin
authors.affiliation: San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas; Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, Texas.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lange
authors.affiliation: San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas; Florida Atlantic University, Department of Chemistry and Biochemistry, Jupiter, Florida.
authors.forename: Dorota
authors.initials: D
authors.lastname: Tokmina-Roszyk
authors.affiliation: San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas; Florida Atlantic University, Department of Chemistry and Biochemistry, Jupiter, Florida.
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Fields
authors.affiliation: Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center, San Antonio, Texas; Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina. Electronic address: decastrobrasl14@ecu.edu.
authors.forename: Lisandra E
authors.initials: LE
authors.lastname: de Castro Brás
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002921:Cicatrix; D024042:Collagen Type I / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D000090602:Collagen Type I, alpha 1 Chain; D004353:Drug Evaluation, Preclinical; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011897:Random Allocation; D020257:Ventricular Remodeling; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C000604174:p1158-59 peptide, human; D020780:Matrix Metalloproteinase 9
keywords: MMP; collagen; extracellular matrix; matricyrptin; proteomics; remodeling