Dataset Information

Application of simultaneous spleen and liver perfusion to the study of reverse cholesterol transport.

ABSTRACT: 1. A new method to isolate and perfuse the rat spleen and liver simultaneously with a common blood perfusate at high haematocrit was developed. The spleen was pre-labelled with [3H]cholesterol, enabling reverse cholesterol transport from an extrahepatic tissue to the blood and thence to the liver and bile to be studied in a single preparation in vitro. 2. The presence of the liver significantly increased the release of [3H]cholesterol from the spleen by 15%, compared with experiments where the spleen was perfused alone. 3. There was a substantial release of [3H]cholesterol and cholesterol mass from the spleen to serum lipoproteins, the majority (80%) to high-density lipoprotein (HDL), in which cholesteryl ester accumulated. 4. The HDL subfractions HDL2 and HDL3 (d 1.085-1.250) were most important for removal of cholesterol from the spleen, whereas HDL1 and HDL2 (d 1.050-1.125) were important for delivery of cholesterol to the liver, a net uptake of cholesteryl ester occurring only from these fractions. 5. Approximately half of the [3H]cholesterol released by the spleen was recovered in erythrocytes. Also, in experiments utilizing a lipoprotein-free perfusate containing erythrocytes, a substantial quantity of [3H]cholesterol was transported and/or exchanged into the liver and bile, indicating that erythrocytes play an important role in the equilibration of unesterified cholesterol between the tissues.

SUBMITTER: Mindham MA

PROVIDER: S-EPMC1137211 | biostudies-other | 1994 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:OBJECTIVE:Hepatic ATP binding cassette transporter A1 (ABCA1) expression is critical for maintaining plasma high-density lipoprotein (HDL) concentrations, but its role in macrophage reverse cholesterol transport and atherosclerosis is not fully understood. We investigated atherosclerosis development and reverse cholesterol transport in hepatocyte-specific ABCA1 knockout (HSKO) mice in the low-density lipoprotein (LDL) receptor KO (LDLrKO) C57BL/6 background. APPROACH AND RESULTS:Male and female LDLrKO and HSKO/LDLrKO mice were switched from chow at 8 weeks of age to an atherogenic diet (10% palm oil, 0.2% cholesterol) for 16 weeks. Chow-fed HSKO/LDLrKO mice had HDL concentrations 10% to 20% of LDLrKO mice, but similar very low-density lipoprotein and LDL concentrations. Surprisingly, HSKO/LDLrKO mice fed the atherogenic diet had significantly lower (40% to 60%) very low-density lipoprotein, LDL, and HDL concentrations (50%) compared with LDLrKO mice. Aortic surface lesion area and cholesterol content were similar for both genotypes of mice, but aortic root intimal area was significantly lower (20% to 40%) in HSKO/LDLrKO mice. Although macrophage (3)H-cholesterol efflux to apoB lipoprotein-depleted plasma was 24% lower for atherogenic diet-fed HSKO/LDLrKO versus LDLrKO mice, variation in percentage efflux among individual mice was <2-fold compared with a 10-fold variation in plasma HDL concentrations, suggesting that HDL levels, per se, were not the primary determinant of plasma efflux capacity. In vivo reverse cholesterol transport, resident peritoneal macrophage sterol content, biliary lipid composition, and fecal cholesterol mass were similar between both genotypes of mice. CONCLUSIONS:The markedly reduced plasma HDL pool in HSKO/LDLrKO mice is sufficient to maintain macrophage reverse cholesterol transport, which, along with reduced plasma very low-density lipoprotein and LDL concentrations, prevented the expected increase in atherosclerosis.

Dataset Information

Application of simultaneous spleen and liver perfusion to the study of reverse cholesterol transport.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure