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CURRENT ISSUETHE JOURNAL OF CARDIOVASCULAR SURGERY

A Journal on Cardiac, Vascular and Thoracic Surgery

Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,632

Frequency: Bi-Monthly

ISSN 0021-9509

Online ISSN 1827-191X

 

The Journal of Cardiovascular Surgery 1998 February;39(1):1-7

VASCULAR PAPERS 

    ORIGINAL ARTICLES

The activ­ity of c-­myb anti­sense oli­go­nu­cleo­tide to pre­vent inti­mal hyper­pla­sia is non­spe­cif­ic

Castier Y., Chemla E., Nierat J.**, Heudes D.*, Vasseur M. A., Rajnoch Ch., Bruneval P.*, Carpentier A., Fabiani J. N.

From ­the Department of Cardiovascular Surgery,
* Department of Anatomopathology, Broussais Hospital, Paris, France
** Roussel-Uclaf Laboratories, Paris, France

Background. We ­sought to deter­mine ­the effi­ca­cy ­and spec­i­fic­ity of a ­new c-­myb anti­sense by inhib­it­ing neo­in­ti­mal hyper­pla­sia in a ­rat abdom­i­nal aor­ta inju­ry mod­el. Using c-­myb anti­sense oli­go­nu­cleo­tides, inhi­bi­tion of vas­cu­lar ­smooth mus­cle ­cell pro­life­ra­tion ­has ­been report­ed.
Methods. Sixty-­six ­male Wistar ­rats ­had a de-en­do­the­lial­iza­tion of ­the abdom­i­nal aor­ta. Following a dou­ble ­blind ran­dom­iza­tion pro­to­col, F127 plu­ron­ic ­gel con­tain­ing ­one of ­the ­five oli­go­nu­cleo­tides or ­plain ­gel ­was ­applied ­around ­the aor­ta: 1) 18-­mer
c-­myb anti­sense (AS18) ­with ­four con­tig­u­ous gua­no­sines (G-quar­tet); 2) 15-­mer c-­myb anti­sense (AS15) with­out G-quar­tet; 3) 1-bp mis­match AS15 with­out G-quar­tet (MM1); 4) an oli­go­nu­cleo­tide ­with G-quar­tet (4G), where­as ­the oth­er bas­es ­were cho­sen at ran­dom; 5) 1-bp mis­match 4G with­out G-quar­tet (MM2). After 21 ­days ­all ­rats ­were sac­ri­ficed ­and aor­tas har­vest­ed ­for his­to­mor­pho­met­ric eval­u­a­tion. Four ­rats ­were giv­en flu­o­res­cent-­labeled oli­go­nu­cleo­tides to ­study in ­vivo local­iza­tion ­after ­local adven­tial deliv­ery.
Results. Morphometric anal­y­sis ­showed sig­nif­i­cant sup­pres­sion of neo­in­ti­mal hyper­pla­sia in AS18 ­and 4G ­and MM2 ­groups com­pared ­with ­GEL, AS15 ­and MM1 ­groups (p<0.05). The oli­go­nu­cleo­tide-­labeled aor­tas ­showed pen­e­tra­tion of ­the oli­go­nu­cleo­tides ­into ­the ­media ­which ­increased ­with ­time.
Conclusions. Our find­ings point­ed to ­the poten­tial ­non spec­i­fic­ity of ­the c-­myb anti­sense oli­go­nu­cleo­tide in ­vivo. Such ­results ­will min­i­mize ­the impor­tance of anti­sense strat­e­gy as a poten­tial ther­a­peu­tic ­for pre­vent­ing neo­in­ti­mal hyper­pla­sia. The ­two oli­go­nu­cleo­tides ­with a G-quar­tet inhib­it­ed neo­in­ti­mal hyper­pla­sia in ­our mod­el. Exploring a ­non-anti­sense mech­a­nism, G-quar­tet oli­go­nu­cleo­tides as poten­tial ­drugs to ­reduce neo­in­ti­mal hyper­pla­sia is attrac­tive.

language: English


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