Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency

Increased secretion and levels of ApoB-containing lipoproteins (BLp) common ly occur in familiar hyperlipidemia, obesity and diabetes. The plasma phosp holipid-transfer protein (PLTP) is known to mediate transfer of phospholipi ds between BLp and HDL during their intravascular metabolism. To address a possible role of PLTP in dyslipidemia and atherogenesis, we bred mice defic ient in the gene encoding PLTP (PLTP-deficient mice) using different hyperl ipidemic mouse strains. In ApoB-transgenic and ApoE-deficient backgrounds, PLTP deficiency resulted in reduced production and levels of BLp and marked ly decreased atherosclerosis. BLp secretion was diminished in hepatocytes f rom ApoB-transgenic PLTP-deficient mice, a defect that was corrected when P LTP was reintroduced in adenovirus. The studies reveal a major, unexpected role of PLTP in regulating the secretion of BLp and identify PLTP as a ther apeutic target.