Biomedical subjects

Maysoon Al-Haideri

Publications and source records attributed to Maysoon Al-Haideri.

4 recordsLinked to original sources

PubMed2003

Enhanced bridging function and augmented monocyte adhesion by lipoprotein lipase N9: insights into increased risk of coronary artery disease in N9 carriers.

Lipoprotein lipase (LPL) is central to triacylglycerol (TG) metabolism, having both hydrolytic and bridging functions. The common LPL gene variant D9N is associated with raised TG, reduced HDL-cholesterol concentrations and increased risk of coronary artery disease (CAD). To investigate the functional basis for the phenotype in N9 carriers, CHO K1 cells were stably transfected with wild type (D9) or mutant (N9) LPL cDNA. LPL RNA expression levels, monomer-to-dimer ratios, and dimer specific activities were similar in D9 and N9 cells. Significantly enhanced binding (4.6-fold) and internalisation (2.6-fold) of 125I-LDL by N9 compared with D9 cells was eradicated by pre-treatment with either heparin or heparinase, confirming involvement of LPL and cell surface proteoglycans. N9 cells bound and internalised 3.8- and 4.4-fold more oxidised 125I-LDL, respectively, than D9 cells (both P<0.0001). Binding of monocytes was 7-fold greater to plates coated with purified LPL-N9 dimer compared with LPL-D9 (P<=0.005). Thus once on the cell surface, LPL-N9 enhances bridging, as assessed both by LDL binding and internalisation, and monocyte adhesion. This augmented LPL-N9 bridging provides a mechanism for the reported increased CAD risk in N9 carriers.

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PubMed2002

Apolipoprotein E and lipoprotein lipase increase triglyceride-rich particle binding but decrease particle penetration in arterial wall.

OBJECTIVE: Liver-derived apolipoprotein E (apoE) decreases atherosclerosis without altering the circulating concentrations of plasma lipoproteins. We evaluated the effects of apoE and lipoprotein lipase (LpL) on the interactions of triglyceride-rich particles (TGRPs) in the arterial wall. METHODS AND RESULTS: Quantitative fluorescence microscopy was used to study the interactions of TGRPs (25- to 35-nm diameter) in the arterial wall. Carotid arteries were harvested from rats, placed in a perfusion chamber, and perfused with fluorescently labeled TGRPs. In the absence of apoE or LpL, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-TGRP (100 microg neutral lipid/mL) was poorly retained in the arterial wall. The addition of either apoE (10 microg/mL) or LpL (10 microg/mL) increased TGRP accumulation 220% and 100%, respectively. This effect was attenuated by heparin (10.0 IU/mL). Histological analyses of cross sections from these vessels demonstrate that in the absence of apoE or LpL, there is deep penetration of lipid into the arterial wall. With the addition of either apoE or LpL, arterial wall penetration of TGRP is blocked. CONCLUSIONS: These results demonstrate that although apoE and LpL increase arterial wall accumulation of TGRPs, these proteins also reduce the penetration of TGRPs into the arterial wall. We postulate that this may represent a novel antiatherogenic property of apoE and LpL.

Animals↗

PubMed2002

Omega-3 triglycerides modify blood clearance and tissue targeting pathways of lipid emulsions.

Omega-3-rich (n-3) triglycerides (TG) are increasingly recognized as having modulating roles in many physiological and pathological conditions. We questioned whether the catabolism of lipid emulsions would be changed after enrichment with fish oil (n-3) TG as compared to enrichment with omega-6-rich soy oil (n-6) TG. Phospholipid-stabilized emulsions of n-3 TG and n-6 TG were labeled with [(3)H]cholesteryl oleoyl ether and administered by bolus injection to wild-type (WT) mice, mice lacking the low-density lipoprotein receptor (LDL-R) (LDL-R -/-), and apolipoprotein E (apoE) knockout mice (apoE -/-). The effects of exogenous apoE, heparin, Triton WR 1339, and lactoferrin on catabolism of emulsions were also assayed. n-3 TG emulsions were cleared faster from blood and had different extrahepatic tissue targeting compared to n-6 TG emulsions. In apoE -/- and LDL-R -/- mice, blood clearance of n-6 TG emulsions slowed with decreased liver uptake, but no changes were observed in n-3 TG emulsion clearance and tissue uptake compared to WT mice. In WT mice, addition of exogenous apoE to the emulsion increased liver uptake of n-6 TG emulsions but had no impact on n-3 TG emulsions. Pre-injection of heparin increased and Triton WR 1339 and lactoferrin decreased blood clearance of n-6 TG emulsions with little or no effect on n-3 TG emulsions. Liver uptake of n-6 TG emulsions increased after heparin injection and decreased after Triton WR 1339 injection, but uptake of n-3 TG emulsions was not changed. These data show that the catabolism of n-3 TG emulsions and the catabolism of n-6 TG emulsions occur via very different mechanisms. Removal of chylomicron-sized n-6 TG emulsions is modulated by lipoprotein lipase (LPL), apoE, LDL-R, and lactoferrin-sensitive pathways. In contrast, clearance of chylomicron-sized n-3 TG emulsions relies on LPL to a very minor extent and is independent of apoE, LDL-R, and lactoferrin-sensitive pathways.

Animals↗

PubMedDate not supplied

Effects of particle size on blood clearance and tissue uptake of lipid emulsions with different triglyceride compositions.

BACKGROUND: Particle size of IV lipid emulsions affects the catabolism of long-chain triglyceride (LCT) emulsions, but little is known about its effect on the catabolism of medium-chain triglyceride (MCT)- and fish oil (FO)-containing emulsions. METHODS: Large (VLDL size), intermediate, and small (IDL size) emulsions with different triglyceride (TG) compositions were labeled with [3H]cholesteryl oleoyl ether: LCT (triolein 100%), MCT:LCT (trioctanoin:triolein 50%:50%), MCT:LCT:FO (trioctanoin:triolein:triDHA 50%:40%:10%), and FO (triDHA 100%). Emulsions (0.4 mg TG/mouse) were injected into C57BL/6J mice, and blood clearance and tissue uptake of emulsion particles were determined. RESULTS: Large emulsion particles had 2- to 3-fold faster fractional catabolic rates (FCR) compared with small particles with the same TG content. There was 1.5- to 2.0-fold higher FCR of large FO-containing emulsions (FO and MCT:LCT:FO) compared with large LCT and MCT:LCT emulsions, whereas effects of FO on FCR in small emulsions were not observed. Large FO-containing emulsions were taken up more by adipose tissue compared with small particles with concomitant decreases in hepatic uptake. Preinjection of heparin reduced heart and adipose uptakes of FO and MCT:LCT:FO emulsions with increased uptake by liver, suggesting a role of lipoprotein lipase in catabolism of FO-containing emulsions. CONCLUSIONS: In a mouse model, FO addition to large emulsions increased blood clearance and changed organ delivery. In contrast, there was no or little effect when particle size became smaller. We hypothesize that in humans, FO addition to lipid emulsions can help target emulsion delivery to certain extrahepatic tissues, a factor that may be of use for delivering specific fatty acids, or even drugs, to specific organs.

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