Document Detail

Proteinases and plaque rupture: unblocking the road to translation.
MedLine Citation:
PMID:  25089553     Owner:  NLM     Status:  Publisher    
PURPOSE OF REVIEW: To review progress over the past 5 years in relating extracellular proteinases to plaque rupture, the cause of most myocardial infarctions, and consider the most promising prospects for developing related treatments.
RECENT FINDINGS: Cysteinyl cathepsins have been implicated in multiple macrophage functions that could promote plaque rupture. Cathepsin K is an attractive target because it is a collagenase and selective inhibitors are already being used in phase III clinical trials. Several serine proteinases clearly influence vascular remodelling and atherogenesis but important, unrelated actions limit their value as therapeutic targets. Among the metalloproteinases, new evidence supports roles for A Disintigrin and Metalloproteinases (ADAMs), including ADAM-10, ADAM-17 and ADAM-33, which suggest that selective inhibitors might be effective treatments. For ADAMs with ThromboSpondin domains (ADAMTSs), there are biological and genome-wide association data linking ADAMTS-7 to incidence of coronary heart disease but not increased risk of myocardial infarctions. In the case of matrix metalloproteinases (MMPs), selective inhibitors of MMP-12 and MMP-13 are available and may be appropriate for development as therapies. Novel targets, including MMP-8, MMP-10, MMP-14, MMP-19, MMP-25 and MMP-28, are also being considered.
SUMMARY: New opportunities exist to exploit proteinases as therapeutic targets in plaque rupture.
Andrew C Newby
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-31
Journal Detail:
Title:  Current opinion in lipidology     Volume:  -     ISSN:  1473-6535     ISO Abbreviation:  Curr. Opin. Lipidol.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-8-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010000     Medline TA:  Curr Opin Lipidol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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