Method of treating hyperlipidemia and atherosclerosis with mir-30c

Abstract

This disclosure provides a novel role for microRNA (miR) regulation of lipid metabolism via the MTP pathway, leading to reductions in apoB secretion and blood lipid levels. MiR regulation of the MTP pathway is shown herein to reduce hyperlipidemia and atherosclerosis in vivo. Therefore, inhibition of MTP expression and activity by miR regulation is identified as a new therapeutic target for treatment of cardiovascular disease and conditions or diseases associated with cardiovascular disease such as hyperlipidemia, atherosclerosis, and metabolic syndrome. Treatment of cardiovascular disease and associated conditions or diseases with the novel MTP inhibitors of the invention, such as miR-30c homologs or miR-30c agonists, reduces MTP-associated lipid production without side effects that occur with other methods of MTP inhibition.

1 . - 8 . (canceled) 
     
     
         9 . A pharmaceutical composition for the treatment of cardiovascular disease, hyperlipidemia, atherosclerosis, obesity, diabetes, or metabolic syndrome, comprising an effective amount of miR-30c or a miR-30c agonist. 
     
     
         10 . A pharmaceutical composition for the treatment of cardiovascular disease, hyperlipidemia, atherosclerosis, obesity, diabetes, or metabolic syndrome, comprising an effective amount of a miR-30c homolog. 
     
     
         11 . A pharmaceutical composition for treating cardiovascular disease, hyperlipidemia, atherosclerosis, obesity, diabetes, or metabolic syndrome in a subject in need thereof, comprising administration of miR-30c or a miR-30c agonist in an amount effective to treat the disease in said subject wherein administration of the miR-30c or the miR-30c agonist results in avoidance of hepatic steatosis in said subject. 
     
     
         12 . A pharmaceutical composition for reducing serum lipids in a subject in need thereof, comprising administration of miR-30c or a miR-30c agonist in an amount effective to reduce serum lipids in said subject wherein administration of the miR-30c or the miR-30c agonist results in avoidance of hepatic steatosis in said subject. 
     
     
         13 . A pharmaceutical composition for reducing microsomal triglyceride transfer protein (MTP) activity in a subject in need thereof, comprising administration of miR-30c or a miR-30c agonist in an amount effective to reduce MTP activity in said subject wherein administration of the miR-30c or the miR-30c agonist results in avoidance of hepatic steatosis in said subject. 
     
     
         14 . A pharmaceutical composition for reducing lipid or lipoprotein biosynthesis in a subject in need thereof, comprising administration of a miR-30c or a miR-30c agonist in an amount effective to reduce lipid or lipoprotein biosynthesis wherein administration of the miR-30c or the miR-30c agonist results in avoidance of hepatic steatosis in said subject. 
     
     
         15 . The composition of  claim 11 , further comprising administration of at least one additional cholesterol reducing agent. 
     
     
         16 . The composition of  claim 15 , wherein one of the at least one additional cholesterol reducing agents is a statin. 
     
     
         17 . The composition of  claim 12 , further comprising administration of at least one additional cholesterol reducing agent. 
     
     
         18 . The composition of  claim 1 , wherein one of the at least one additional cholesterol reducing agents is a statin. 
     
     
         19 . The composition of  claim 13 , further comprising administration of at least one additional cholesterol reducing agent. 
     
     
         20 . The composition of  claim 19 , wherein one of the at least one additional cholesterol reducing agents is a statin. 
     
     
         21 . A pharmaceutical composition for treating a disease or disorder selected from the group consisting of cardiovascular disease, hyperlipidemia, atherosclerosis, obesity, diabetes, or metabolic syndrome in a subject in need thereof, comprising administration of miR-30c or a miR-30c agonist in an amount effective to reduce the levels of at least one target gene selected from the group consisting of LPGAT1, ELOVL5, MBOAT, IFG1R, ATP8B1, ALG9, LEPR, CHKA, PPARGC1A and StARD3 in said subject, wherein administration of the miR-30c or the miR-30c agonist results in treatment of the disease or disorder. 
     
     
         22 . The composition of  claim 21 , wherein administration of the miR-30c or the miR-30c agonist results in avoidance of steatosis. 
     
     
         23 . A pharmaceutical composition for reducing serum lipids in a subject in need thereof, comprising administration of miR-30c or a miR-30c agonist in an amount effective to reduce the levels of at least one target gene selected from the group consisting of LPGAT1, ELOVL5, MBOAT, IFG 1 R, ATP8B 1, ALG9, LEPR, CHKA, PPARGC 1 A and StARD3 in said subject, wherein administration of the miR-30c or the miR-30c agonist results in reducing serum lipids in said subject. 
     
     
         24 . The composition of  claim 23 , wherein administration of miR-30c or the miR-30c agonist results in avoidance of steatosis. 
     
     
         25 . A pharmaceutical composition for reducing microsomal triglyceride transfer protein (MTP) activity in a subject in need thereof, comprising administration of a miR-30c or a miR-30c agonist in an amount effective to reduce the levels of at least one target gene selected from the group consisting of LPGAT1, ELOVL5, MBOAT, IFG1R, ATP8B1, ALG9, LEPR, CHKA, PPARGC1A and StARD3 in said subject, wherein administration of the miR-30c or the miR-30c agonist results in reduced MTP activity in said subject. 
     
     
         26 . The composition of  claim 25 , wherein administration of the miR-30c or a miR-30c agonist results in avoidance of steatosis. 
     
     
         27 . A pharmaceutical composition for reducing lipid or lipoprotein biosynthesis in a subject in need thereof, comprising administration of a miR-30c or a miR-30c agonist in an amount effective to reduce the levels of at least one target gene selected from the group consisting of LPGAT1, ELOVL5, MBOAT, IFG1R, ATP8B1, ALG9, LEPR, CHKA, PPARGC1A and StARD3 in said subject, wherein administration of the miR-30c or the miR-30c agonist results in reduced lipid or lipoprotein biosynthesis in said subject. 
     
     
         28 . The composition of  claim 27 , wherein administration of the miR-30c or the miR-30c agonist results in avoidance of steatosis.