1 Division of Nephrology, Department of Medicine, University of California, Irvine, Irvine, California 92697; and 2 Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157
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ABSTRACT |
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Lecithin-cholesterol acetyltransferase (LCAT) is involved in the synthesis of plasma cholesteryl esters and is pivotal in the maturation of plasma high-density lipoprotein (HDL) and conversion of HDL3 to HDL2. In nephrotic syndrome (NS), the ratio of HDL2 to HDL3 is low even though the total concentration of HDL is generally normal. We hypothesize that the reduced HDL2/HDL3 ratio in NS is due to urinary losses of LCAT, leading to plasma LCAT deficiency. To test this hypothesis, Sprague-Dawley rats were randomized to NS (given 130 mg puromycin aminonucleoside on day 1 and 60 mg ip on day 14) or control groups and were studied on day 30. To dissect the effect of proteinuria from hypoalbuminemia, a group of Nagase rats with inherited hypoalbuminemia was included. Hepatic LCAT and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA abundance and plasma and urine LCAT activity were measured. The NS group showed a fourfold rise in serum cholesterol and triglycerides, a fivefold rise in free cholesterol, and a fourfold fall in the HDL-to-total cholesterol ratio. Despite severe hypoalbuminemia, the Nagase rats showed only a mild elevation of serum cholesterol and triglycerides with a normal serum free cholesterol and HDL-to-total cholesterol ratio. The NS group exhibited a normal hepatic LCAT-to-GAPDH mRNA ratio, a marked reduction in plasma LCAT activity, and a significant increase in urinary LCAT excretion. LCAT/GAPDH mRNA and plasma and urine LCAT were normal in Nagase rats. Thus NS led to heavy urinary losses and reduced plasma concentration of LCAT, despite normal hepatic LCAT mRNA abundance. However, hypoalbuminemia, per se, without proteinuria as seen in the Nagase rats had no effect on plasma LCAT or the HDL-to-total cholesterol ratio. Therefore, proteinuria, not hypoalbuminemia, causes LCAT deficiency and a depressed HDL-to-total cholesterol ratio in NS.
proteinuria; hyperlipidemia; hypercholesterolemia; hypoalbuminemia; hypertriglyceridemia; arteriosclerosis; high- density lipoprotein
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INTRODUCTION |
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LECITHIN-CHOLESTEROL ACYLTRANSFERASE (LCAT) is a 63-kDa glycoprotein enzyme that is synthesized in the liver and secreted in plasma (10, 43) where it catalyzes the removal of the fatty acyl group from the sn-2 position of lecithin and its transfer to free cholesterol to form cholesteryl ester (13). Thus the enzyme possesses a phospholipase A2-like activity and an acyltransferase activity. The enzymatic activity of LCAT depends on the presence of apolipoprotein a-1, which serves as its cofactor (3, 9). LCAT plays a central role in cholesterol uptake by high-density lipoprotein (HDL) particles from the peripheral tissues and maturation of HDL to cholesterol ester-rich HDL2 particles (12). Inherited LCAT deficiency is associated with a marked reduction in HDL-mediated reverse cholesterol transport, a depressed ratio of cholesterol-rich HDL2 to cholesterol-poor HDL3, the presence of cholesterol-laden foam cells in various tissues, accelerated atherosclerotic cardiovascular disease, corneal opacification, and progressive renal disease (20).
Heavy glomerular proteinuria, otherwise known as nephrotic syndrome (NS), is associated with profound hyperlipidemia. Nephrotic hyperlipidemia is characterized by hypercholesterolemia, hypertriglyceridemia, and elevations of low-density (LDL) and very-low-density (VLDL) lipoproteins as well as lipoprotein (a) (5, 44). Although HDL levels are generally normal, the maturation of cholesterol-poor HDL3 to cholesterol-rich cardiovascular protective HDL2 is impaired in NS (18, 32). Because LCAT is necessary for maturation of HDL and generation of HDL2, we hypothesized that this phenomenon may be indicative of urinary losses of LCAT and acquired LCAT deficiency in NS. The present study was designed to test this hypothesis.
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METHODS |
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Study groups.
Male Sprague-Dawley rats weighing 180-200 g were housed in a
temperature- and light-controlled space with 12:12-h light (500 lux)-dark (5 lux) cycles. The rats were allowed free access to food
(Purina Rat Chow, Purina Mills, Brentwood, MO) and water. Animals were
randomized into the nephrotic (NS) and normal control groups. The rats
assigned to the NS group received sequential intraperitoneal injections
of puromycin aminonucleoside on day 1 (130 mg/kg) and
day 14 (60 mg/kg). The rats assigned to the control group
received placebo injections of 5% dextrose in water. In an attempt to
dissect the possible effect of proteinuria from that of
hypoalbuminemia, a group of male age-matched Nagase hypoalbuminemic rats (Japan SLC, Hamamatsu, Japan) was included as well. Thirty days
after the initial puromycin or placebo injections, animals (n = 6/group) were placed in individual metabolic cages
for a 24-h urine collection. The next day, under general anesthesia (50 mg/kg ip Nembutal), the animals were killed between the hours of 9 and
11 AM, and the liver was removed immediately, frozen in liquid
nitrogen, and stored at
70°C for subsequent processing. In
addition, blood was collected using cardiac puncture.
RNA preparation and Northern blot analysis.
Total RNA was prepared from 0.2 g of frozen liver tissue with
RNazol using the manufacturer's recommended procedure (Tel-Test, Friendswood, TX). RNA concentration was determined from the absorbance at 260 nm using a spectrophotometer (Gene-Quat; Bio-Rad, Hercules, CA).
Aliquots of total RNA (25 µg) were denatured in 2.2 M formaldehyde at
65°C for 15 min and run on 1% agarose-2.2 M formaldehyde gels at 40 volts for 5 h. The separated RNA was transferred to the nylon
membrane (Zeta probe; Bio-Rad) by capillary blotting in 6 × 0.9 M NaCl
and 0.09 sodium citrate (pH = 7.0) overnight and immobilized
by ultraviolet irradiation (Ultraviolet Crosslinker; Fisher
Scientific, Pittsburgh, PA). The membrane was incubated at 65°C in a
solution containing 5× 0.75 M NaCl, 0.05 M
NaH2PO4, and 0.005 M EDTA (pH 7.4; SSPE), 5×
Denhardt's [Ficoll (type 400), polyvinylpyrrolidone, BSA (fraction 5)
1 g/l each], 1% SDS, and 100 µg/ml salmon sperm DNA for 2 h.
The cDNA probe for rat LCAT (1.35 kb EcoR I and
Hind II fragment of R1P1) was
supplied by Parks, and rat glyceraldehyde phosphate dehydrogenase
(GAPDH; 1.3 kb Pst I fragment) was obtained from American
Type Culture Collection (Rockville, MD). Both probes were labeled with
[32P]dCTP (3,000 Ci/mmol; NEN, Boston, MA) by the random
primer method (Promega, Madison, WI). Hybridization was carried out at
65°C in a prehybridization solution with 32P-labeled
cDNA. The blots were washed two times in 2× SSPE-0.5% SDS solution at
room temperature, two times in 1× SSPE-0.5% SDS solution at 37°C,
and two times in 0.1× SSPE-0.5% SDS solution at 65°C for 15 min
each. The washed blots were exposed to X-ray film (NEN) at 80°C for
6 h for GAPDH and 2 days for LCAT. The autoradiographs were
scanned with a laser densitometer (Molecular Dynamics, Sunnyvale, CA)
to determine relative mRNA levels. The values obtained for GAPDH were
used as the internal control.
LCAT activity assay.
LCAT incubations were performed in duplicate using an exogenous
substrate assay as described previously (29). The
exogenous substrate consisted of recombinant HDL (rHDL) particles
containing sn-1(16:0), sn-2(20:4) phosphatidylcholine,
[3H]cholesterol, and human apolipoprotein A-I made by
cholate dialysis (14). Assays of initial reaction velocity
were performed in 0.5 ml buffer (10 mM Tris, 140 mM NaCl, 0.01% EDTA,
and 0.01% NaN3, pH 7.4) containing rHDL (1.2 µg
cholesterol; saturating substrate concentration), 0.6% BSA (fatty
acid-free; Sigma, St. Louis, MO), 2 mM -mercaptoethanol, and 5 µl
rat plasma as a source of LCAT. Incubations were performed for 15 min,
after which the free and esterified cholesterol radiolabel was
extracted and quantified (27).
Miscellaneous assays. Urine protein concentration was determined by a quantitative colorimetric assay using a kit purchased from Sigma. Serum albumin concentration was quantified by the bromocresol green method employing a kit purchased from Wako Diagnostics and Chemicals (Richmond, VA). A colorimetric assay was used to measure serum and urine creatinine concentrations using a kit obtained from Sigma Chemical. Plasma concentrations of total cholesterol and free cholesterol were measured by enzymatic colorimetric assays using kits supplied by Wako Diagnostics and Chemicals. Plasma HDL and LDL cholesterol concentrations and triglyceride level were determined by kits purchased from Sigma.
Data analysis. ANOVA, Duncan's multiple range test, and regression analysis were performed for statistical analysis of the data, which are presented as means ± SE. P values <0.05 were considered statistically significant.
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RESULTS |
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General findings.
As expected, both nephrotic and hypoalbuminemic Nagase rats exhibited
marked hypoalbuminemia compared with the control group (Table
1). Hypoalbuminemia was associated with
severe proteinuria in the nephrotic group. However, urinary protein
excretion was normal in the Nagase rats. No significant difference was
found in either serum creatinine concentration or creatinine clearance among the three groups. The NS group showed a 4-fold elevation of serum
total cholesterol, a 5-fold rise in plasma free cholesterol, a nearly
4.5-fold increase in serum triglyceride concentration, and a 50%
reduction in the serum HDL cholesterol-to-total cholesterol concentration ratio compared with the control group. However, serum
cholesterol and triglyceride concentrations were only mildly elevated,
and the HDL cholesterol-to-total cholesterol ratio and plasma free
cholesterol were normal in the Nagase rats despite extreme
hypoalbuminemia.
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Plasma and urine LCAT activities.
The nephrotic animals exhibited a marked fourfold reduction in plasma
LCAT activity coupled with a fourfold increase in urine LCAT excretion
when compared with the normal control group. In contrast, despite
severe hypoalbuminemia, the Nagase rats showed normal plasma and
urinary LCAT values (Fig. 1). Plasma LCAT
activity was inversely related to urine LCAT activity
(r = 0.95, P < 0.001) and urine
protein excretion (r =
0.86, P < 0.005). No correlation was found between plasma LCAT activity and serum
albumin concentration among the study animals (Fig.
2).
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Hepatic LCAT mRNA.
Despite severe reduction in plasma LCAT activity, hepatic tissue LCAT
mRNA was normal in the NS group. Likewise, hepatic LCAT mRNA abundance
was unchanged in the Nagase rats (Fig.
3). Thus the reduction in plasma LCAT
activity in the NS group was not due to its diminished transcript
abundance in the liver.
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DISCUSSION |
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NS is associated with marked hyperlipidemia and profound
abnormalities of cholesterol and triglyceride metabolisms. In an earlier study, we found a marked upregulation of hepatic
3-hydroxy-3-glutaryl-CoA (HMG-CoA) reductase (the rate-limiting
step in cholesterol biosynthesis) during the induction phase of NS and
its inappropriate elevation during the chronic phase of NS in rats
(36). We subsequently found an inappropriately low
expression of hepatic cholesterol 7-hydroxylase (the rate-limiting
enzyme in cholesterol catabolism to bile acids) in the nephrotic rats
(26). Despite severe hypercholesterolemia, the nephrotic
rats employed in the latter studies showed normal hepatocyte
cholesterol concentrations, which contrasted the marked elevation of
hepatocyte cholesterol content in the control rats with diet-induced
hypercholesterolemia of equal magnitude (26, 36). Because
intracellular, not extracellular, cholesterol is involved in regulation
of HMG-CoA reductase and cholesterol 7
-hydroxylase expression
(30, 42), we supposed that the lack of a rise in intracellular cholesterol in the face of severe hypercholesterolemia may account for the failure of the liver to suppress biosynthetic and
stimulate catabolic pathways of cholesterol metabolism in the nephrotic
animals. Moreover, we hypothesized that the apparent discordance
between the intracellular and extracellular compartments in the liver
with respect to cholesterol may be due to impaired hepatic cholesterol
uptake from the circulation. To test this hypothesis in a series of
subsequent experiments, expressions of LDL receptor and scavenger
receptor class B type I (SR-BI), which represent the principal pathways
of cholesterol uptake by the liver, were studied. These studies
revealed marked downregulations of hepatic LDL receptor and SR-BI
proteins with normal mRNA abundance in both instances (25,
37). The above studies explored the effect of NS on hepatic
metabolism of cholesterol but did not address cholesterol
esterification and uptake from the peripheral tissues. In a series of
separate studies designed to explore the molecular basis of the
NS-induced abnormalities of triglyceride-rich lipoproteins (4, 5,
18, 21), we found marked downregulation of lipoprotein lipase,
hepatic triglyceride lipase, and VLDL receptor expression in nephrotic
rats (22-24).
The present study revealed a marked reduction in plasma LCAT activity in NS rats, denoting a severe acquired deficiency state. The reduction in plasma LCAT activity in the NS group was accompanied by heavy urinary losses of the enzyme. However, LCAT mRNA abundance in the liver tissue was not altered by NS. Plasma LCAT activity was inversely related to its urinary excretion. Taken together these findings suggest that the urinary losses must have contributed to the observed LCAT deficiency in NS, a condition characterized by urinary losses of proteins of intermediate molecular weight. The molecular weight of LCAT (63 kDa) is very close to that of albumin, whose urinary losses and depressed plasma concentration constitute the defining features of NS. Thus it is not surprising that, as with albumin, urinary losses can lead to a low plasma concentration of LCAT. In fact, urinary losses have been shown to result in the reduction of plasma concentrations of numerous other proteins and protein-bound agents in this condition. These include but are not limited to hormone and hormone-binding proteins (1, 6, 19, 35, 45), coagulation and fibrinolytic factors (33, 34, 39-41), IgG, metal-binding proteins (8), etc.
It should be noted that the effect of NS on metabolism of plasma proteins is usually not limited to their losses in the urine. In fact, NS frequently affects biosynthesis and catabolism of many proteins. (17) Available data on LCAT metabolism are extremely limited, and information on the tissue uptake and catabolism of LCAT is lacking. LCAT appears to be constitutively secreted by the liver, and very few perturbations are known to affect LCAT biosynthesis, except inflammatory mediators (7) and chronic renal failure (38). While demonstrating urinary losses of LCAT, we have not explored its biosynthesis and catabolism in the present study. Similarly, we have not examined the possible effect of the nephrotic milieu on LCAT activity. Further studies are required to elucidate LCAT metabolism in health and disease in general and the specific issues relevant to NS, noted above.
In an attempt to dissect the possible role of proteinuria from that of hypoalbuminemia, we included a group of Nagase rats with inherited hypoalbuminemia and no proteinuria. In contrast to the nephrotic animals, the Nagase rats showed normal plasma and urine LCAT activity. These observations suggested that LCAT deficiency in the NS group was not due to hypoalbuminemia, which was common to both NS and Nagase rats, but rather was related to proteinuria, which was present in the former but not the latter group.
Cholesterol content of the peripheral cells is a function of the combined cholesterol influx and de novo synthesis on the one hand and cholesterol efflux on the other. The primary pathway of cholesterol influx in the peripheral tissues is the LDL receptor pathway. The principal pathway for removal of surplus cholesterol from the peripheral cells is cholesterol uptake and its disposal in the liver by HDL. Optimal cholesterol uptake by HDL depends on the presence of LCAT, which catalyzes the removal of a fatty acyl group from the sn-2 position of lecithin and its transfer to free cholesterol to form cholesterol ester. Because of its increased hydrophobicity, cholesterol ester formed on the surface of HDL particles then partitions into the lipid core of HDL (12). This process helps to maintain a favorable gradient for continued diffusion of free cholesterol from the cell to the surface of HDL (11, 13). However, in the presence of LCAT deficiency, accumulation of unprocessed free cholesterol on the surface of HDL limits the gradient-driven cholesterol uptake by HDL. Consequently, maturation of cholesterol-poor HDL3 to cholesterol ester-rich HDL2 diminishes, the HDL2-to-HDL3 ratio falls, and cellular cholesterol rises (20). The functional significance of the observed LCAT deficiency is evidenced by marked elevation of plasma free cholesterol and the reduction in the HDL-to-total cholesterol ratio in the NS animals.
On the basis of the above observations, severe LCAT deficiency shown here can contribute to the previously known abnormalities of HDL maturation and metabolism (18, 32) in NS. This is further compounded by the recent demonstration in NS of acquired deficiency of SR-BI, which facilitates hepatic uptake of lipids from HDL particles (25). Together these findings point to a profound dysregulation of HDL metabolism and hence impaired reverse cholesterol transport in NS.
The observed reduction in plasma LCAT enzymatic activity found here in rats with puromycin-induced NS is consistent with the earlier reports in rats with Haymann nephritis (31) and humans with NS (28) and contrasts the results reported by other investigators who have shown either normal or elevated LCAT activity (15, 32). The reason for the observed disparity is uncertain and may be due to methodological differences.
In conclusion, NS results in profound deficiency and urinary losses of LCAT. The observed LCAT deficiency is related to proteinuria but not hypoalbuminemia. This phenomenon can contribute to the reported abnormalities of HDL metabolism in NS.
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ACKNOWLEDGEMENTS |
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This work was supported, in part, by National Heart, Lung, and Blood Institute Grant HL-54176 (J. S. Parks).
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FOOTNOTES |
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Address for reprint requests and other correspondence: N. D. Vaziri, Div. of Nephrology, UCI Medical Center, 101 The City Dr., Bldg. 53, Rm. 125, Rt. 81, Orange, CA 92868.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 24 July 2000; accepted in final form 4 January 2001.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Afrasiabi, MA,
Vaziri ND,
Gwinup G,
Mays DM,
Barton CH,
Ness RL,
and
Valenta LJ.
Thyroid function studies in the nephrotic syndrome.
Ann Intern Med
90:
335-338,
1979[ISI][Medline].
2.
Agbedana, ED,
Yamamoto T,
Moriwaki Y,
Suda M,
Takahashi S,
and
Higashimo K.
Studies on abnormal lipid metabolism in experimental nephrotic syndrome.
Nephron
64:
256-261,
1993[ISI][Medline].
3.
Akanuma, Y,
Yokoyama S,
Imawari M,
and
Itakura H.
A role of ApoA-1 in LCAT reaction.
Scand J Clin Lab Invest Suppl
150:
40-47,
1978[Medline].
4.
Davies, RW,
Staprans I,
Hutchison FN,
and
Kaysen GA.
Proteinuria, not altered albumin metabolism, affects hyperlipidemia in the nephrotic rat.
J Clin Invest
86:
600-605,
1990[ISI][Medline].
5.
de Sain-van der Velden, MG,
Kaysen GA,
Barrett HA,
Stellaard F,
Gadellaa MM,
Voorbij HA,
Reijngoud DJ,
and
Rabelink TJ.
Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis.
Kidney Int
53:
994-1001,
1998[ISI][Medline].
6.
Elias, AN,
Carreon G,
Vaziri ND,
Pandian MR,
and
Oveisi F.
The pituitary-gonadal axis in experimental nephrotic syndrome in male rats.
J Lab Clin Med
120:
949-954,
1992[ISI][Medline].
7.
Ettinger, WH,
Miller LD,
Albers JJ,
and
Parks JS.
Lipopolysaccharide and tumor necrosis factor cause a fall in plasma concentration of lecithin: cholesterol acyltransferase in cynomoglus monkeys.
J Lipid Res
31:
1099-1107,
1990[Abstract].
8.
Falk, RH,
Jennette JC,
and
Nachman PH.
Nephrotic syndrome.
In: Brenner and Rector's the Kidney, edited by Brenner BM.. Philadelphia, PA: Saunders, 2000, p. 1266-1271.
9.
Fielding, CJ,
Shore VG,
and
Fielding PE.
A protein cofactor of lecithin:cholesterol acyltransferase.
Biochem Biophys Res Commun
46:
1493-1498,
1972[ISI][Medline].
10.
Francone, OL,
and
Fielding CJ.
Structure-function relationships in human lecithin:cholesterol acyltransferase. Site-directed mutagenesis at serine residues 181 and 216.
Biochemistry
30:
10074-10077,
1991[ISI][Medline].
11.
Francone, OL,
Gurakar A,
and
Fielding C.
Distribution and functions of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in plasma lipoproteins. Evidence for a functional unit containing these activities together with apolipoproteins A-I and D that catalyzes the esterification and transfer of cell-derived cholesterol.
J Biol Chem
264:
7066-7072,
1989
12.
Genest, J, Jr,
Marcil M,
Denis M,
and
Yu L.
High density lipoproteins in health and in disease.
J Investig Med
47:
31-42,
1999[ISI][Medline].
13.
Glomset, JA.
The plasma lecithins:cholesterol acyltransferase reaction.
J Lipid Res
9:
155-167,
1968
14.
Huggins, KW,
Curtiss LK,
Gebre AK,
and
Parks JS.
Effect of long chain polyunsaturated fatty acids in the sn-2 position of phosphatidylcholine on the interaction with recombinant high density lipoprotein apolipoprotein A-I.
J Lipid Res
39:
2423-2431,
1998
15.
Joles, JA,
Willekes-Koolschijim N,
Scheek LM,
Koomans HA,
Rabelink TJ,
and
Van Tol A.
Lipoprotein phospholipid composition and LCAT activity in nephrotic and analbuminemic rats.
Kidney Int
46:
97-104,
1994[ISI][Medline].
16.
Karayan, L,
Qiu S,
Betard C,
Dufour R,
Roederer G,
Minnich A,
Davignon J,
and
Genest J, Jr.
Response to HMG CoA reductase inhibitor in heterozygous familial hypercholesterolemia due to 10-Kb deletion ("French Canadian Mutation") of LDL receptor gene.
Arterioscler Thromb
14:
1258-1263,
1994[Abstract].
17.
Kaysen, GA.
The metabolism of serum proteins in nephrosis.
Am Kidney Found Nephrol Lett
5:
31-46,
1988.
18.
Kaysen, GA,
and
de Sain-van der Velden MG.
New insights into lipid metabolism in the nephrotic syndrome.
Kidney Int Suppl
71:
S18-S21,
1999[Medline].
19.
Khamiseh, G,
Vaziri ND,
Oveisi F,
Ahmadnia MR,
and
Ahmadnia L.
Vitamin D absorption, plasma concentration and urinary excretion of 25-hydroxyvitamin D in nephrotic syndrome.
Proc Soc Exp Biol Med
196:
210-213,
1991[Abstract].
20.
Kuivenhoven, JA,
Pritchard H,
Hill J,
Frohlich J,
Assmann G,
and
Kastelein J.
The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes.
J Lipid Res
38:
191-205,
1997[Abstract].
21.
Levy, E,
Ziv E,
Bar-On H,
and
Shafrir E.
Experimental nephrotic syndrome: removal and tissue distribution of chylomicrons and very-low-density lipoproteins of normal and nephrotic origin.
Biochim Biophys Acta
1043:
259-266,
1990[ISI][Medline].
22.
Liang, K,
and
Vaziri ND.
Gene expression of lipoprotein lipase in experimental nephrosis.
J Lab Clin Med
130:
387-394,
1997[ISI][Medline].
23.
Liang, K,
and
Vaziri ND.
Acquired VLDL receptor deficiency in experimental nephrosis.
Kidney Int
51:
1761-1765,
1997[ISI][Medline].
24.
Liang, K,
and
Vaziri ND.
Down-regulation of hepatic lipase expression in experimental nephrotic syndrome.
Kidney Int
51:
1933-1937,
1997[ISI][Medline].
25.
Liang, K,
and
Vaziri ND.
Down-regulation of hepatic high-density lipoprotein receptor, SR-B1, in nephrotic syndrome.
Kidney Int
56:
621-626,
1999[ISI][Medline].
26.
Liang, KH,
Oveisi F,
and
Vaziri ND.
Gene expression of hepatic cholesterol 7 alpha-hydroxylase in the course of puromycin-induced nephrosis.
Kidney Int
49:
855-860,
1996[ISI][Medline].
27.
Miller, KR,
Wang J,
Sorci-Thomas M,
Anderson RA,
and
Parks JS.
Glycosylation structure and enzyme activity of lecithin:cholesterol acyltransferase from human plasma, HepG2 cells, and baculoviral and Chinese hamster ovary cell expression systems.
J Lipid Res
37:
551-561,
1996[Abstract].
28.
Nayak, SS,
Bhaskaranand N,
Kamath KS,
Baliga M,
Venkatesh A,
and
Aroor AR.
Serum apolipoproteins A and B, lecithin: cholesterol acyltransferase activities and urinary cholesterol levels in nephrotic syndrome patients before and during steroid treatment.
Nephron
54:
234-239,
1990[ISI][Medline].
29.
Parks, JS,
and
Gebre AK.
Long-chain polyunsaturated fatty acids in the sn-2 position of phosphatidylcholine decrease the stability of recombinant high density lipoprotein apolipoprotein A-I and the activation energy of the lecithin:cholesterol acyltransferase reaction.
J Lipid Res
38:
266-275,
1997[Abstract].
30.
Russell, DW,
and
Setchell KD.
Bile acid biosynthesis.
Biochemistry
31:
4737-4749,
1992[ISI][Medline].
31.
Sestak, TL,
Alavi N,
and
Subbaiah PV.
Plasma lipids and acyltransferase activities in experimental nephrotic syndrome.
Kidney Int
36:
240-248,
1989[ISI][Medline].
32.
Subbaiah, PV,
and
Rodby RA.
Abnormal acyltransferase activities and accelerated cholesteryl ester transfer in patients with nephrotic syndrome.
Metabolism
43:
1126-1133,
1994[ISI][Medline].
33.
Vaziri, ND,
Gonzales E,
Barton CH,
Chen HT,
Nguyen Q,
and
Arquilla M.
Factor XIII and its substrates, fibronectin, fibrinogen, and alpha 2-antiplasmin, in plasma and urine of patients with nephrosis.
J Lab Clin Med
117:
152-156,
1991[ISI][Medline].
34.
Vaziri, ND,
Gonzales EC,
Shayestehfar B,
and
Barton CH.
Plasma levels and urinary excretion of fibrinolytic and protease inhibitory proteins in nephrotic syndrome.
J Lab Clin Med
124:
118-124,
1994[ISI][Medline].
35.
Vaziri, ND,
Kaupke CJ,
Barton CH,
and
Gonzales E.
Plasma concentration and urinary excretion of erythropoietin in adult nephrotic syndrome.
Am J Med
92:
35-40,
1992[ISI][Medline].
36.
Vaziri, ND,
and
Liang KH.
Hepatic HMG-CoA reductase gene expression during the course of puromycin-induced nephrosis.
Kidney Int
48:
1979-1985,
1995[ISI][Medline].
37.
Vaziri, ND,
and
Liang KH.
Down-regulation of hepatic LDL receptor expression in experimental nephrosis.
Kidney Int
50:
887-893,
1996[ISI][Medline].
38.
Vaziri ND, Liang K, and Park JS. Down regulation of hepatic
lecithin: Cholesterol acyltransferase (LCAT) gene expression in chronic
renal failure. Kidney Int. In press.
39.
Vaziri, ND,
Ngo JL,
Ibsen KH,
Mahalwas K,
Roy S,
and
Hung EK.
Deficiency and urinary losses of factor XII in adult nephrotic syndrome.
Nephron
32:
342-346,
1982[ISI][Medline].
40.
Vaziri, ND,
Paule P,
Toohey J,
Hung E,
Alikhani S,
Darwish R,
and
Pahl MV.
Acquired deficiency and urinary excretion of antithrombin III in nephrotic syndrome.
Arch Intern Med
144:
1802-1803,
1984[Abstract].
41.
Vaziri, ND,
Toohey J,
Paule P,
Hung E,
Darwish R,
Barton CH,
and
Alikhani S.
Urinary excretion and deficiency of prothrombin in nephrotic syndrome.
Am J Med
77:
433-436,
1984[ISI][Medline].
42.
Vlahcevic, ZR,
Heuman DM,
and
Hylemon PB.
Regulation of bile acid synthesis.
Hepatology
13:
590-600,
1991[ISI][Medline].
43.
Wang, J,
Gebre AK,
Anderson RA,
and
Parks JS.
Cloning and in vitro expression of rat lecithin:cholesterol acyltransferase.
Biochim Biophys Acta
1346:
207-211,
1997[ISI][Medline].
44.
Wanner, C,
Rader D,
Bartens W,
Kramer J,
Brewer HB,
Schollmeyer P,
and
Wieland H.
Elevated plasma lipoprotein(a) in patients with the nephrotic syndrome.
Ann Intern Med
119:
263-269,
1993
45.
Zhou, XJ,
and
Vaziri ND.
Erythropoietin metabolism and pharmacokinetics in experimental nephrosis.
Am J Physiol Renal Fluid Electrolyte Physiol
263:
F812-F815,
1992