[show abstract][hide abstract] ABSTRACT: Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL⁻/⁻) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages.
Hypertriglyceridemic LPL⁻/⁻ mice were lethally irradiated, then transplanted with bone marrow from wild-type (LPL⁺/⁺) or LPL⁻/⁻ mice, respectively. Sixteen weeks later, LPL⁺/⁺ →LPL⁻/⁻ mice displayed significant reduction in plasma levels of triglyceride and cholesterol (408±44.9 vs. 2.7±0.5×10³ and 82.9±7.1 vs. 229.1±30.6 mg/dl, p<0.05, respectively), while a 2.7-fold increase in plasma high density lipoprotein- cholesterol (p<0.01) was observed, compared with LPL⁻/⁻→LPL⁻/⁻ control mice. The clearance rate for the oral fat load test in LPL⁺/⁺ →LPL⁻/⁻ mice was faster than that in LPL⁻/⁻→LPL⁻/⁻ mice, but slower than that in wild-type mice. Liver triglyceride content in LPL⁺/⁺→LPL⁻/⁻ mice was also significantly increased, compared with LPL⁻/⁻→LPL⁻/⁻ mice (6.8±0.7 vs. 4.6±0.5 mg/g wet tissue, p<0.05, n = 6). However, no significant change was observed in the expression levels of genes involved in hepatic lipid metabolism between the two groups.
Hematopoietic cell-derived LPL could efficiently ameliorate severe hypertriglyceridemia and hypo-alpha-cholesterolemia at the compensation of increased triglyceride content of liver in LPL⁻/⁻ mice.
PLoS ONE 01/2011; 6(9):e25620. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Enhanced susceptibility to atherosclerosis from severe hypertriglyceridemia (HTG) resulting from lipoprotein lipase (LPL) deficiency has been demonstrated in our recent findings which employed a unique mouse model. In the present study we provide further evidence that severe HTG due to LPL deficiency also promotes an atherothrombotic response to arterial injury induced by ferric chloride in a severe combined hyperlipidemic mouse model. Methods and results: A mouse model (LPL(-/-)XApoE(-/-) double knockout, DKO) with severe combined hyperlipidemia was established by crossing ApoE and LPL-deficient mice. The common carotid arteries of ApoE knockout (EKO) and DKO mice were subjected to injury by ferric chloride, and the formation of arterial thrombosis together with various markers were compared in these lesions. DKO mice demonstrated significantly enhanced thrombus formation overlying atherosclerotic plaque after injury, which contained smooth muscle cells, macrophages, and neutral lipid. The area of neointima, mean intima/media ratios, and the percentage of luminal stenosis were significantly greater (P<0.01) in DKO mice. Compared with EKO mice, the expression of von Willebrand factor (vWF) and plasminogen activator inhibitor type 1 (PAI-1) were increased in DKO mice. Conclusions: Severe combined hyperlipidemia promotes thrombosis after ferric chloride injury to atherosclerotic vessels and HTG plays a major role in the process.
Biochemical and Biophysical Research Communications 08/2009; 385(4):563-9. · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: In order to make the water distribution network design more scientific and reasonable, the economy and reliability analysis should be considered. Firstly, the cost of pipeline construction is used as one objective. The sum of node surplus head and the node surplus head variance are used as another two objective functions. A multi-objective optimization model in water distribution system is established using a joint. MATLAB and EPANET platform, along with a non-dominated sorting genetic algorithm (NSGA-II) are applied to solve the optimization problem. Finally, a water supply network is employed to demonstrate to the application of this method. It is concluded that the multi-objective optimization model based on the non-dominated sorting genetic algorithm-II performed reasonably and effectively to solve optimization problem for water distribution system.