MICRO-RNAs THAT MODULATE SMOOTH MUSCLE PROLIFERATION AND DIFFERENTIATION

Abstract

The present invention relates to the identification of microRNAs that regulate smooth muscle cell proliferation and differentiation, including the miR-143/miR-145 cluster. Methods of treating restenosis and neointima formation by increasing expression of miR-143 and/or miR-145 are disclosed. The present invention also relates to the identification of two microRNAs, miR-486 and miR-422a, that regulate cell survival in the heart. Methods of treating or preventing cardiac hypertrophy, heart failure, or myocardial infarction by increasing expression of miR-486 and/or miR-422a in heart tissue are also disclosed.

1 - 50 . (canceled) 
     
     
         51 . A composition comprising a coated medical device, wherein said coating comprises a polynucleotide comprising a sequence of miR-143. 
     
     
         52 . The composition of  claim 51 , wherein said polynucleotide comprises a mature sequence of miR-143. 
     
     
         53 . The composition of  claim 52 , wherein said polynucleotide comprises a sequence of SEQ ID NO: 38. 
     
     
         54 . The composition of  claim 52 , wherein said polynucleotide is about 18 to about 25 nucleotides in length. 
     
     
         55 . The composition of  claim 51 , wherein said polynucleotide is double stranded. 
     
     
         56 . The composition of  claim 51 , wherein said polynucleotide is conjugated to cholesterol. 
     
     
         57 . The composition of  claim 51 , wherein said polynucleotide comprises a pri-miRNA or pre-miRNA sequence of miR-143. 
     
     
         58 . The composition of  claim 51 , wherein said medical device is a catheter, balloon, or stent. 
     
     
         59 . The composition of  claim 51 , wherein the coating further comprises an anti-restenosis compound. 
     
     
         60 . The composition of  claim 59 , wherein the anti-restenosis compound is selected from the group consisting of paclitaxel, rapamycin (sirolimus), tacrolimus, zotarolimus, everolimus, docetaxel, pimecrolimus, and derivatives thereof. 
     
     
         61 . The composition of  claim 51 , wherein the polynucleotide is encoded by an expression vector under the transcriptional control of a promoter. 
     
     
         62 . The composition of  claim 61 , wherein the expression vector is a viral vector.