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Title:
Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency | Nature Medicine
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Increased secretion and levels of ApoB-containing lipoproteins (BLp) commonly occur in familial hyperlipidemia, obesity and diabetes. The plasma phospholipid-transfer protein (PLTP) is known to mediate transfer of phospholipids between BLp and HDL during their intravascular metabolism. To address a possible role of PLTP in dyslipidemia and atherogenesis, we bred mice deficient in the gene encoding PLTP (PLTP-deficient mice) using different hyperlipidemic mouse strains. In ApoB-transgenic and ApoE-deficient backgrounds, PLTP deficiency resulted in reduced production and levels of BLp and markedly decreased atherosclerosis. BLp secretion was diminished in hepatocytes from ApoB-transgenic PLTP-deficient mice, a defect that was corrected when PLTP was reintroduced in adenovirus. The studies reveal a major, unexpected role of PLTP in regulating the secretion of BLp and identify PLTP as a therapeutic target.
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nature portfolio permissions reprints privacy policy advertising increased high-density lipoprotein nature 342 nature 496 nature social media plasma phospholipid-transfer protein phospholipid-transfer protein deficiency author information authors bactericidal/permeability-increasing protein development adenovirus-mediated gene delivery 131i-labeled plasma proteins author correspondence apob-transgenic pltp-deficient mice phospholipid transfer protein apolipoprotein e-deficient mouse personal data high density lipoproteins markedly decreased atherosclerosis chylomicron-sized lipid particles phospholipid transfer activity anna skoldΒ &Β xiao xiao data protection springerlink instant access permissions atherosclerotic cardiovascular disease lipid-transfer function cholesterol transport protein gene-targeted mice article jiang privacy bred mice deficient stable isotope technique gene encoding pltp coronary heart disease insulin-dependent diabetes pltp-deficient mice explore content subscription content hyperlipidemic mouse strains apoe-deficient backgrounds mice lacking apolipoprotein european economic area pltp deficiency resulted institutional subscriptions read frame stop codon
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description:Increased secretion and levels of ApoB-containing lipoproteins (BLp) commonly occur in familial hyperlipidemia, obesity and diabetes. The plasma phospholipid-transfer protein (PLTP) is known to mediate transfer of phospholipids between BLp and HDL during their intravascular metabolism. To address a possible role of PLTP in dyslipidemia and atherogenesis, we bred mice deficient in the gene encoding PLTP (PLTP-deficient mice) using different hyperlipidemic mouse strains. In ApoB-transgenic and ApoE-deficient backgrounds, PLTP deficiency resulted in reduced production and levels of BLp and markedly decreased atherosclerosis. BLp secretion was diminished in hepatocytes from ApoB-transgenic PLTP-deficient mice, a defect that was corrected when PLTP was reintroduced in adenovirus. The studies reveal a major, unexpected role of PLTP in regulating the secretion of BLp and identify PLTP as a therapeutic target.
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