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
C6‐ceramide‐coated catheters promote re‐endothelialization of stretch‐injured arteries
Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp:
E-Artikel
Titel:
C6‐ceramide‐coated catheters promote re‐endothelialization of stretch‐injured arteries
Beteiligte:
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
Beschreibung:
<jats:p>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<jats:sub>6</jats:sub>‐ceramide limits arterial stenosis without inhibiting endothelial wound healing responses. C<jats:sub>6</jats:sub>‐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.</jats:p>