title: Liberation of desmosine and isodesmosine as amino acids from insoluble elastin by elastolytic proteases.
abstract: The development of atherosclerotic lesions and abdominal aortic aneurysms involves degradation and loss of extracellular matrix components, such as collagen and elastin. Releases of the elastin cross-links desmosine (DES) and isodesmosine (IDE) may reflect elastin degradation in cardiovascular diseases. This study investigated the production of soluble elastin cross-linking structures by proteinases implicated in arterial diseases. Recombinant MMP-12 and neutrophil elastase liberated DES and IDE as amino acids from insoluble elastin. DES and IDE were also released from insoluble elastin exposed to monocyte/macrophage cell lines or human primary macrophages derived from peripheral blood monocytes. Elastin oxidized by reactive oxygen species (ROS) liberated more unconjugated DES and IDE than did non-oxidized elastin when incubated with MMP-12 or neutrophil elastase. These results support the exploration of free DES and IDE as biomarkers of elastin degradation.
authors: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Hideyuki
authors: H
authors: Umeda
authors: Masanori
authors: M
authors: Aikawa
authors: Peter
authors: P
authors: Libby
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002460:Cell Line; D003895:Desmosine / Q000378:metabolism*; D004549:Elastin / Q000378:metabolism*; D006801:Humans; D007524:Isodesmosine / Q000378:metabolism*; D019272:Leukocyte Elastase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053508:Matrix Metalloproteinase 12 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D003895:Desmosine; D004549:Elastin; D007524:Isodesmosine; D019272:Leukocyte Elastase; D053508:Matrix Metalloproteinase 12