Antisense oligonucleotides have recently been proposed as a pharmacological approach to prevent neointimal hyperplasia following balloon angioplasty. This study reports the significant enhancement on in vivo restenosis prevention conferred by the conjugation of cholesterol to a c-myc antisense oligomer when compared to a non conjugated oligonucleotide. The inhibitory potential of the conjugate was increased 2.4-fold, reaching a reduction of intimal hyperplasia of 84.7 % vs. control arteries. Enhancement of hyperplasia prevention may be related to the 2.7-fold increase in oligomer vascular retention conferred by the cholesterol moieties, sufficient to cover a significant portion of the proliferation window that typically follows balloon angioplasty.
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