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Title: Lysyl oxidase propeptide inhibits smooth muscle cell signaling and proliferation

Lysyl oxidase is required for the normal biosynthesis and maturation of collagen and elastin. It is expressed by vascular smooth muscle cells, and its increased expression has been previously found in atherosclerosis and in models of balloon angioplasty. The lysyl oxidase propeptide (LOX-PP) has more recently been found to have biological activity as a tumor suppressor, and it inhibits Erk1/2 Map kinase activation. We reasoned that LOX-PP may have functions in normal non-transformed cells. We, therefore, investigated its effects on smooth muscle cells, focusing on important biological processes mediated by Erk1/2-dependent signaling pathways including proliferation and matrix metalloproteinase-9 (MMP-9) expression. In addition, we investigated whether evidence for accumulation of LOX-PP could be found in vivo in a femoral artery injury model. Recombinant LOX-PP was expressed and purified, and was found to inhibit primary rat aorta smooth muscle cell proliferation and DNA synthesis by more than 50%. TNF-{alpha}-stimulated MMP-9 expression and Erk1/2 activation were both significantly inhibited by LOX-PP. Immunohistochemistry studies carried out with affinity purified anti-LOX-PP antibody showed that LOX-PP epitopes were expressed at elevated levels in vascular lesions of injured arteries. These novel data suggest that LOX-PP may provide a feedback control mechanism that serves to inhibit properties associatedmore » with the development of vascular pathology.« less
Authors:
; ;  [1] ; ;  [2] ; ;  [1] ; ;  [2] ;  [3]
  1. Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine, Division of Oral Biology, 700 Albany Street, W-210 Boston, MA 02118 (United States)
  2. Department of Biochemistry and the Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118 (United States)
  3. Department of Periodontology and Oral Biology, Boston University Goldman School of Dental Medicine, Division of Oral Biology, 700 Albany Street, W-210 Boston, MA 02118 (United States), E-mail: trackman@bu.edu
Publication Date:
OSTI Identifier:
21043602
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 366; Journal Issue: 1; Other Information: DOI: 10.1016/j.bbrc.2007.11.116; PII: S0006-291X(07)02527-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AFFINITY; ANTIBODIES; AORTA; ARTERIOSCLEROSIS; BIOSYNTHESIS; CELL PROLIFERATION; COLLAGEN; CONTROL SYSTEMS; DNA; IN VIVO; INJURIES; MUSCLES; NEOPLASMS; OXIDASES; PATHOLOGY; RATS