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C6‐ceramide‐coated catheters promote re‐endothelialization of stretch‐injured arteries
Author(s) -
O’Neill Sean Michael,
Olympia Dina K,
Fox Todd,
Brown J. Tony,
Stover Thomas C.,
Houck Kristy,
Wilson Ronald,
Waybill Peter,
Kozak Mark,
Kester Mark
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.914.9
Subject(s) - ceramide , medicine , angioplasty , vascular smooth muscle , artery , wound healing , cardiology , chemistry , smooth muscle , surgery , biochemistry , apoptosis
The objective of the present study is to elucidate the biological mechanism(s) by which direct, acute application of growth arresting ceramide analogues leads to a reduction in arterial injury after angioplasty. Immunohistochemical studies in rabbit and porcine coronary, carotid, iliac, and renal models suggest that C 6 ‐ceramide limits arterial stenosis without inhibiting endothelial wound healing responses. C 6 ‐ceramide‐coated balloon catheters reduce internal elastica injury, with a corresponding reduction in medial fracture length in a 28‐day porcine coronary artery stretch model. We investigated if differential metabolism of exogenous ceramide by coronary endothelial and smooth muscle cells could explain the apparent discrepancy between the anti‐proliferative actions of ceramide and the pro‐wound healing responses to ceramide. Human coronary artery endothelial cells, in contrast to human coronary artery smooth muscle cells, preferentially express ceramide kinase and form ceramide‐1‐phoshphate which promoted endothelial cell survival. The combinatorial actions of C6‐ceramide‐coated catheters to limit vascular smooth muscle proliferation and promote re‐endothelialization argue for therapeutic efficacy as adjuncts to stent‐based modalities or as a stand‐alone treatment. These studies were funded by NIH RO1 HL076789 to MK as well as by Reva Medical, San Diego California.