title: Diminished macrophage cholesterol removal rate by the altered HDL metabolism in the Nagase analbuminemic rat.
abstract: Dyslipoproteinemia of the Nagase analbuminemic rat (NAR) is characterized by elevated concentrations of VLDL and LDL attributed to increased rates of liver lipoprotein synthesis. Increased lysophosphatidylcholine (LPC) in NAR HDL has been attributed to high plasma LCAT activity. We show here that, as compared with Sprague-Dawley rats (SDR), NAR plasma triacylglycerol (TAG), total cholesterol (TC), HDL TAG, protein, total phospholipids (PL), LPC, and PS are increased. These alterations rendered the NAR HDL particle more susceptible to the activity of the enzyme hepatic lipoprotein lipase (HL), which otherwise was unaltered in our study. Fractional catabolic rates in blood of the autologous 125I-apoHDL (median and lower quartile values), were, respectively, 0.231 and 1.645 (n = 10) in NAR as compared with 0.140 and 0.109 (n = 10) in SDR (P = 0.012), corresponding to synthesis rates of HDL protein of 89.8 +/- 33.7 mg/d in NAR and 17.4 +/- 6.5 mg/d in SDR (P = 0.0122). Furthermore, Swiss mouse macrophage free-cholesterol (FC) efflux rates, measured as the percent [14C]-cholesterol efflux/6 h, were 8.2 +/- 2.3 (n = 9) in NAR HDL and 11.2 +/- 3.2 (n = 10) in SDR HDL (P = 0.03). Therefore, in NAR the modification of the HDL composition slows down the cell FC efflux rate, and together with the increased rate of plasma HDL metabolism influences the reverse cholesterol transport system.
authors.affiliation: Lipids Laboratory (LIM 10), Faculty of Medical Sciences, University of São Paulo, São Paulo, Brazil. catanozi@usp.br
authors.forename: Sergio
authors.initials: S
authors.lastname: Catanozi
authors.forename: Jussara C
authors.initials: JC
authors.lastname: Rocha
authors.forename: Marisa
authors.initials: M
authors.lastname: Passarelli
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Mesquita
authors.forename: Vivian Y
authors.initials: VY
authors.lastname: Suguiama
authors.forename: Maria L
authors.initials: ML
authors.lastname: Guzzo
authors.forename: Antônio
authors.initials: A
authors.lastname: dos Santos Filho
authors.forename: Eder C R
authors.initials: EC
authors.lastname: Quintão
authors.forename: Edna R
authors.initials: ER
authors.lastname: Nakandakare
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D001692:Biological Transport / Q000235:genetics; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D006951:Hyperlipoproteinemias / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000172:deficiency*; D014280:Triglycerides / Q000097:blood
chemical_list: D001053:Apolipoproteins; C034396:HDL-triglyceride; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL; D012709:Serum Albumin; D014280:Triglycerides; D002784:Cholesterol