Methods and compositions for treating atherosclerosis

Abstract

In some aspects, the invention provides a method of treating atherosclerosis in a subject. The method comprises administering to the subject an agent that increases the activity or level of a let-7 miRNA or an agent that decreases activity or level of a TGFβ signaling polypeptide in an endothelial cell in the subject. In some embodiments, the subject is administered an additional agent comprising a therapeutically effective amount of rapamycin or any derivative thereof. In some embodiments, the agent is a let-7 miRNA. In some other aspects, the invention provides a pharmaceutical composition comprising a let-7 miRNA. In some embodiments, the let-7 miRNA is encapsulated in a nanoparticle formulated for selective delivery to an endothelial cell.

1 - 53 . (canceled) 
     
     
         54 . A method of reducing an atherosclerotic lesion in a subject, the method comprising administering to the subject a nanoparticle formulated for delivery to an endothelial cell, the nanoparticle comprising an inhibitory RNA that directly decreases in an endothelial cell in the subject the activity or level of a endothelial TGFβ signaling polypeptide selected from the group consisting of TGFβR1 and TGFβR2, thereby reducing or inhibiting the atherosclerotic lesion in the subject. 
     
     
         55 . The method according to  claim 54 , wherein the inhibitory polynucleotide is an siRNA. 
     
     
         56 . The method according to  claim 54 , wherein the nanoparticle is a 7C1 nanoparticle. 
     
     
         57 . A method of inhibiting progression of atherosclerosis in a subject, the method comprising administering to the subject a nanoparticle formulated for delivery to an endothelial cell, the nanoparticle comprising an inhibitory RNA that directly decreases in an endothelial cell in the subject the activity or level of a TGFβ signaling polypeptide selected from the group consisting of TGFβR1 and TGFβR2, thereby inhibiting progression of atherosclerosis in the subject. 
     
     
         58 . The method according to  claim 57 , wherein the inhibitory polynucleotide is an siRNA. 
     
     
         59 . The method according to  claim 57 , wherein the nanoparticle is a 7C1 nanoparticle. 
     
     
         60 . A method of reversing atherosclerosis in a subject, the method comprising administering to the subject a nanoparticle formulated for delivery to an endothelial cell, the nanoparticle comprising an inhibitory RNA that directly decreases in an endothelial cell in the subject the activity or level of a TGFβ signaling polypeptide selected from the polypeptide selected from the group consisting of TGFβR1 and TGFβR2, thereby reversing atherosclerosis in the subject. 
     
     
         61 . The method according to  claim 60 , wherein the inhibitory polynucleotide is an siRNA. 
     
     
         62 . The method according to  claim 60 , wherein the nanoparticle is a 7C1 nanoparticle. 
     
     
         63 . A method of treating atherosclerosis in a subject, the method comprising administering to the subject a nanoparticle formulated for delivery to an endothelial cell, the nanoparticle comprising an inhibitory RNA that directly decreases in an endothelial cell in the subject the activity or level of a TGFβ signaling polypeptide selected from the group consisting of TGFβR1 and TGFβR2, thereby treating atherosclerosis in the subject. 
     
     
         64 . The method according to  claim 63 , wherein the inhibitory polynucleotide is an siRNA. 
     
     
         65 . The method according to  claim 63 , wherein the nanoparticle is a 7C1 nanoparticle.