Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice
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چکیده
منابع مشابه
Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol.
BACKGROUND Proprotein convertase subtilisin kexin type 9 (PCSK9) is gaining attention as a key regulator of serum LDL-cholesterol (LDLC). This novel serine protease causes the degradation of hepatic LDL receptors by an unknown mechanism. In humans, gain-of-function mutations in the PCSK9 gene cause a form of familial hypercholesterolemia, whereas loss-of-function mutations result in significant...
متن کاملGene inactivation of proprotein convertase subtilisin/kexin type 9 reduces atherosclerosis in mice.
BACKGROUND The proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes independently of its enzymatic activity the degradation of the low-density lipoprotein (LDL) receptor. PCSK9 gain of function in humans leads to autosomal dominant hypercholesterolemia, whereas the absence of functional PCSK9 results in ≈7-fold lower levels of LDL cholesterol. This suggests that lowering PCSK9 may pro...
متن کاملA proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. We have generated a neutralizing anti-PCSK9 antibody, mAb1, that binds to an epitope on PCSK9 adjacent to the region required for LDLR interaction. In vitro, mAb1 inhibits PCSK9 binding to the LDLR a...
متن کاملPlasma proprotein convertase subtilisin/kexin type 9: a marker of LDL apolipoprotein B-100 catabolism?
BACKGROUND Experimental studies suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important regulator of LDL metabolism because of its ability to facilitate degradation of the LDL receptor. We investigated the association between plasma PCSK9 concentration and LDL apolipoprotein B-100 (apo B-100) metabolism in men with a wide range of body mass index values. METHODS We ...
متن کاملStatins, plasma proprotein convertase subtilisin/kexin type 9 concentrations, and LDL lowering.
The discovery in 2003 that variants in the PCSK9 (proprotein convertase subtilisin/kexin type 9) gene cause autosomal dominant hypercholesterolemia revealed a new aspect of LDL cholesterol (LDL-C) metabolism (1). PCSK9, a protein of 692 amino acid residues produced at high concentrations in the liver, kidney, and intestine, has profound effects on LDL-C concentrations (2). Both gain-of-function...
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ژورنال
عنوان ژورنال: Journal of Lipid Research
سال: 2007
ISSN: 0022-2275
DOI: 10.1194/jlr.c600025-jlr200