ライフサイエンスコーパス: LCAT

1 LCAT activity was lowest in patients with proinflammator

2 LCAT and apoE contents of CETP-D HDL-2 were markedly inc

3 LCAT beneficially alters the plasma concentrations of ap

4 LCAT bound to (3)H-free cholesterol (FC)-labeled pre-bet

5 LCAT deficiency reduced the plasma high density lipoprot

6 LCAT deficiency resulted in a 12-fold increase in the ra

7 LCAT deficiency resulted in significant reductions in th

8 LCAT is activated through an unknown mechanism by apolip

9 LCAT reactivity was impaired by apoA-ISeattle nascent HD

10 LCAT(+/-) mice had normal RCT despite a significant redu

11 LCAT-KO mice had normochromic normocytic anemia with inc

12 LCAT-null parasites have impaired growth in vitro, reduc

13 HDL (fractional catabolic rate in days(-1): LCAT-Tg = 3.7 +/- 0.34, LCATxCETP-Tg = 6.1 +/- 0.16, and

14 -ray crystallographic analysis of the 2.45 A LCAT-27C3 complex shows that 27C3 binding does not induc

15 To test this hypothesis, ACAT2-/- LCAT-/- LDLr-/-, ACAT2-/- LDLr-/-, and LCAT-/- LDLr-/- m

16 e total plasma cholesterol (TPC) of ACAT2-/- LCAT-/- LDLr-/- mice was 67% lower because of the comple

17 lux was normal, and the capacity to activate LCAT in vitro was reduced by 53%.

18 by MPO impairs apoA-I's ability to activate LCAT in vitro.

19 the ability of wild-type apoA-I to activate LCAT in vivo.

20 reductase restored HDL's ability to activate LCAT.

21 compared with their counterparts with active LCAT.

22 ctivate lecithin:cholesterol acyltranserase (LCAT) was approximately 70-80% of the wild-type (WT) con

23 ted in lecithin:cholesterol acyltransferase (LCAT) activation or lipid binding.

24 ingly, lecithin:cholesterol acyltransferase (LCAT) activation results correlate qualitatively with th

25 P) and lecithin cholesterol acyltransferase (LCAT) activities were decreased by more than 80%, sugges

26 Lecithin:cholesterol acyltransferase (LCAT) activity was measured by a commercially available

27 fected lecithin:cholesterol acyltransferase (LCAT) activity.

28 uch as lecithin cholesterol acyltransferase (LCAT) and acyl CoA acyltransferase (ACAT).

29 d that lecithin:cholesterol acyltransferase (LCAT) and LDL receptor double knock-out mice (Ldlr(-/-)x

30 ion by lecithin/cholesterol acyltransferase (LCAT) and transfer by cholesteryl ester transfer protein

31 tivate lecithin:cholesterol acyltransferase (LCAT) as compared to the WT control.

32 2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of

33 ate of lecithin:cholesterol acyltransferase (LCAT) catalyzed cholesterol esterification.

34 Lecithin:cholesterol acyltransferase (LCAT) catalyzes the formation of plasma cholesteryl este

35 d that lecithin-cholesterol acyltransferase (LCAT) contributes significantly to the apoB lipoprotein

36 s that lecithin:cholesterol acyltransferase (LCAT) deficiency would accelerate atherosclerosis develo

37 ing of lecithin-cholesterol acyltransferase (LCAT) function.

38 A1 and lecithin cholesterol acyltransferase (LCAT) gene loci.

39 human lecithin cholesterol acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density

40 tivate lecithin/cholesterol acyltransferase (LCAT) in vitro.

41 ity of lecithin-cholesterol acyltransferase (LCAT) is affected differentially by the location and ext

42 ion of lecithin-cholesterol acyltransferase (LCAT) is cholesterol esterification, our previous studie

43 enzyme lecithin:cholesterol acyltransferase (LCAT) is cholesteryl ester (CE).

44 Lecithin:cholesterol acyltransferase (LCAT) is the major determinant of the cholesteryl ester

45 d that lecithin:cholesterol acyltransferase (LCAT) knock-out mice, particularly in the LDL receptor k

46 Lecithin:cholesterol acyltransferase (LCAT) plays a key role in reverse cholesterol transport

47 ecause lecithin:cholesterol acyltransferase (LCAT) possesses intrinsic PAF-AH-like activity, it also

48 of the lecithin-cholesterol acyltransferase (LCAT) reaction.

49 plasma lecithin:cholesterol acyltransferase (LCAT) substrate reactivity was decreased, LCAT specific

50 n with lecithin-cholesterol acyltransferase (LCAT) the enzyme for which apoA-I acts as a cofactor.

51 Lecithin:cholesterol acyltransferase (LCAT) then drives the conversion of nascent HDL to spher

52 ing of lecithin cholesterol acyltransferase (LCAT) to lipoprotein surfaces is a key step in the rever

53 sis in lecithin cholesterol acyltransferase (LCAT) transgenic (Tg) mice, similar to results previousl

54 ted by lecithin-cholesterol acyltransferase (LCAT) which is produced in the liver.

55 ion of lecithin-cholesterol acyltransferase (LCAT) with apolipoprotein A-I (apoA-I) plays a critical

56 malian lecithin:cholesterol acyltransferase (LCAT), a key enzyme that produces cholesteryl esters via

57 nzyme lecithin: cholesterol acyltransferase (LCAT), and by other enzyme(s) with unknown identity.

58 ut not lecithin-cholesterol acyltransferase (LCAT), and to differ from humans in retinal expression o

59 enzyme lecithin:cholesterol acyltransferase (LCAT), catalyzing the rapid conversion of lipoprotein ch

60 y with lecithin-cholesterol acyltransferase (LCAT), compared with rHDL particles made with control ap

61 P) and lecithin:cholesterol acyltransferase (LCAT), on chromosome 16q; and for the LDL receptor (LDLR

62 or B1, lecithin:cholesterol acyltransferase (LCAT), or apoA-I in the liver did not stimulate choleste

63 human lecithin-cholesterol acyltransferase (LCAT), T123I and N228K, were expressed in COS-1 and Chin

64 Human lecithin-cholesterol acyltransferase (LCAT), which is normally specific for the sn-2 position

65 ent on lecithin:cholesterol acyltransferase (LCAT), which rapidly converts cholesterol to cholesteryl

66 plasma lecithin-cholesterol acyltransferase (LCAT).

67 T1 and lecithin:cholesterol acyltransferase (LCAT).

68 enzyme lecithin cholesterol acyltransferase (LCAT).

69 y with lecithin:cholesterol acyltransferase (LCAT).

70 ity of lecithin:cholesterol acyltransferase (LCAT).

71 human lecithin-cholesteryl acyltransferase (LCAT) that has elevated HDL and increased diet-induced a

72 increase in overall hydrophobicity, affects LCAT activation.

73 Although LCAT activity does become rate limiting in the context o

74 F) region, and proposed that it serves as an LCAT docking site.

75 correlation between plasma LCAT activity and LCAT content.

76 The behavior of PAF-AH and LCAT in hepatobiliary inflammatory responses in vivo has

77 ced three candidate genes (ABCA1, APOA1, and LCAT) that cause Mendelian forms of low HDL-C levels in

78 olipoprotein A-I as the lipid emulsifier and LCAT activator.

79 ure HDL was observed when ABCA1 function and LCAT activities were restored.

80 re critical for both LCAT binding to HDL and LCAT catalytic efficiency.

81 aortic lesion formation in both apoE-KO and LCAT-Tg mice, without changing the plasma lipid profile,

82 deficiency on macrophage RCT, LCAT(-/-) and LCAT(+/-) mice were compared with wild-type mice.

83 T2-/- LCAT-/- LDLr-/-, ACAT2-/- LDLr-/-, and LCAT-/- LDLr-/- mice were fed a 0.15% cholesterol diet f

84 ce (25, 7, and 12%; p < 0.001 of normal) and LCAT +/- mice (65 and 59%; p < 0.001 and 81%; not signif

85 s NS-induced LDL receptor, HDL receptor, and LCAT deficiencies; improves plasma lipid profile; and am

86 s necessary for both DMPC solubilization and LCAT activation.

87 apoE-KO x HL-KO mice, as well as LCAT-Tg and LCAT-Tg x HL-KO mice, chimeric for macrophage HL gene ex

88 l signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH).

89 ApoE-/- LCAT-/- mice fed the atherogenic diet, compared with apo

90 icle size and events critical to RCT such as LCAT activation and lipid-free apoA-I production for ABC

91 apoE-KO and apoE-KO x HL-KO mice, as well as LCAT-Tg and LCAT-Tg x HL-KO mice, chimeric for macrophag

92 al processes as ABC1-regulated HDL assembly, LCAT activation, receptor binding, reverse lipid transpo

93 oA-I helix 6 interact directly and attenuate LCAT activation, independent of the overall particle cha

94 (-) plasma retained (1)/(3) the amount of B6 LCAT activity.

95 rse correlation (r = 0.85) was found between LCAT catalytic efficiency and apoA-I helix 6 net negativ

96 cular rationale for the relationship between LCAT glycosylation and activity.

97 nd Asp(168)) of apoA-I are critical for both LCAT binding to HDL and LCAT catalytic efficiency.

98 genesis in cholesterol-depleted SC from both LCAT-KO and SKO mice.

99 esterol, HDL cholesterol, and apoA-I in both LCAT -/- mice (25, 7, and 12%; p < 0.001 of normal) and

100 u or Asn), which showed preservation in both LCAT binding affinity and catalytic efficiency.

101 To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice.

102 s, the esterification rate of cholesterol by LCAT was only 15% greater than for sitosterol.

103 kage was observed at the MnSOD (P=.02), CETP/LCAT (P=.03), and apolipoprotein AI-CIII-AIV loci (P=.00

104 els of high-density lipoprotein cholesterol, LCAT-deficient mice had only a 50% reduction in RCT.

105 ome rate limiting in the context of complete LCAT deficiency, RCT is reduced by only 50% even in the

106 transcript represents 5-20% of the complete LCAT message in cultured fibroblasts and liver.

107 e (LCAT) substrate reactivity was decreased, LCAT specific activity increased, and plasma LCAT protei

108 the reaction of HDL with LCAT by decreasing LCAT binding to hybrid particles and making the enzyme a

109 The assay accurately detects LCAT activity in buffer and in plasma that is depleted o

110 3 weeks on a high-fat high-cholesterol diet, LCAT -/- mice had significantly lower plasma concentrati

111 the prebeta1-HDL particles by the endogenous LCAT.

112 n future clinical trials in CHD and familial LCAT deficiency patients.

113 in LCAT cause fish eye disease and familial LCAT deficiency.

114 beneficial for CHD, as well as for familial LCAT deficiency, a rare disorder of low HDL-C.

115 and renal abnormalities similar to familial LCAT deficiency patients will permit future evaluation o

116 sing each of the constructs were assayed for LCAT cholesterol esterification (CE) or phospholipase A2

117 for providing an essential conformation for LCAT catalyzed generation of cholesterol esters.

118 165-186 (repeats 6 and 7) are essential for LCAT activation.

119 ese results demonstrate a novel function for LCAT in the detoxification of polar PCs generated during

120 CAT-KO) SC with DKO SC identified a role for LCAT deficiency in priming SC to express BAT genes.

121 RO6 rHDL were a less effective substrate for LCAT.

122 o facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanis

123 clearance and liver uptake of [(3)H]CE from LCAT-Tg HDL.

124 serine, aspartate, and histidine (SDH) from LCAT enzymes.

125 Serum from LCAT-deficient mice had increased ability to promote ABC

126 Serum from LCAT-overexpressing mice had reduced ability to promote

127 transferase (LCAT) deficiency, we generated LCAT knockout (KO) mice and cross-bred them with apolipo

128 l linkers coupled with oligoethylene glycol (LCAT-OEG).

129 metry in rHDL is a critical factor governing LCAT activation.

130 ll as the liver uptake of [(3)H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) i

131 erol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1

132 Human LCAT overexpression in human apolipoprotein A-I transgen

133 Human LCAT prefers phosphatidylcholine (PC) with sn-1-palmitoy

134 pressing either of the two mutants and human LCAT normalized the plasma apoA-I, HDL cholesterol level

135 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potenti

136 acids at sn-1 also were transferred by human LCAT at a higher rate (5-75% of total) than they were tr

137 n of mice with adenoviruses expressing human LCAT and the helix 6P mutant dramatically increased plas

138 eviously described a point mutation in human LCAT (E to A at residue 149; hE149A) that demonstrated g

139 Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immu

140 s, and pharmacodynamics of recombinant human LCAT (ACP-501).

141 tein changes indicate that recombinant human LCAT favorably alters HDL metabolism and support recombi

142 HDL metabolism and support recombinant human LCAT use in future clinical trials in CHD and familial L

143 al specificity (30-95% from sn-1) than human LCAT (15-83% from sn-1).

144 construct retained a ratio similar to human LCAT (<0.6).

145 ave been used to study the details of apoA-I-LCAT-catalyzed cholesterol ester formation.

146 dation of a single Met in apoA-I in impaired LCAT activation, a critical early step in reverse choles

147 AT(Tg/Tg), apoA-I(-/-) mice, showed impaired LCAT activation in vivo, with significant reduction in H

148 , LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice.

149 t CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of L

150 igh cholesterol diets, expression of CETP in LCAT-Tg mice reduced total cholesterol (-39% and -13%, r

151 cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunction

152 oes not induce notable structural changes in LCAT.

153 ation of hepatic LDLr and apoE expression in LCAT-KO mice.

154 in the development of glomerulosclerosis in LCAT deficiency.

155 possible treatment for glomerulosclerosis in LCAT-deficient states.

156 tein (VLDL) resulted in a 3-fold increase in LCAT CER, whereas addition of apoA-I resulted in a more

157 ntestinal tract, whereas plasma increases in LCAT and PAF-AH may promote elimination of excess PAF an

158 duced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency

159 derlying human disease for most of the known LCAT missense mutations, and paves the way for rational

160 Mice lacking LCAT have decreased levels of PREG esters in the adrenal

161 calories from palm oil) consumption, LDLr-/- LCAT-/- double knockout mice, compared with LDLr-/- mice

162 lipoprotein cholesterol ester to the liver, LCAT overexpression still had no effect on RCT.

163 he 80 A diameter rHDL showed a 12-fold lower LCAT catalytic efficiency when compared to 96 A diameter

164 refore, we speculate that the 5-6-fold lower LCAT reactivity in 10F6 compared with wild-type apoA-I r

165 transesterification activity than mammalian LCAT.

166 cithin:cholesterol acyltransferase-mediated (LCAT-mediated) cholesteryl ester formation in media.

167 cholesterol acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HD

168 re incubated with purified recombinant mouse LCAT; LDL particles from B6 and apoA-I(-)(/)(-) plasma w

169 hroism in the alpha-helical content of N384Q LCAT and in the beta-sheet content of N84Q LCAT, compare

170 Q LCAT and in the beta-sheet content of N84Q LCAT, compared with wild-type LCAT.

171 rmal and chemical denaturation studies, N84Q LCAT was found to be significantly less stable than wild

172 The N84Q LCAT mutant did not possess measurable enzymatic activit

173 ues 146-160 and/or 220-242 partake in normal LCAT activation and that cooperative interactions betwee

174 mined by the SPR method indicate that normal LCAT dissociates from rHDL, on average, after one cataly

175 hat the negative charge at amino acid 149 of LCAT is a critical determinant for the specificity of th

176 s reduced by only 50% even in the absence of LCAT.

177 in supporting HDL binding and activation of LCAT are debated.

178 Activation of LCAT by apolipoprotein (apo) A-I on nascent (discoidal)

179 rearrangements of HDL, and the activation of LCAT.

180 necessary for lipid binding or activation of LCAT.

181 The physiological activator of LCAT is apolipoprotein A-I (apoA-I), the major HDL prote

182 that apoE is a more significant activator of LCAT than apoA-I on mouse apoB lipoproteins.

183 and apoA-I are the only major activators of LCAT in mouse plasma.

184 letion of helix 6 on the in vivo activity of LCAT and the biogenesis of HDL.

185 due 160 of apoA-I to the in vivo activity of LCAT and the subsequent maturation of HDL and explain th

186 o and substantially enhances the activity of LCAT from humans and cynomolgus macaques.

187 stigate the binding kinetics and affinity of LCAT for lipoproteins.

188 Analysis of LCAT activity in plasmas from control subjects and sickl

189 Analysis of LCAT transgenic animals has established the importance o

190 In conclusion, the association of LCAT to lipoprotein surfaces is essentially independent

191 After attachment of LCAT to discoidal HDL, the helix 5/5 domains in apoA-I f

192 The availability of LCAT-KO mice characterized by lipid, hematologic, and re

193 the buffer decreased k(a) for the binding of LCAT to apoA-I rHDL.

194 ndent pathway due to an increased content of LCAT and apoE.

195 How the deficiency of LCAT activity, observed in all patients studied, contrib

196 We hypothesized that deletion of LCAT and ACAT2 would lead to absence of plasma CEs and r

197 rostatic contribution, while dissociation of LCAT from lipoproteins is decreased due to the presence

198 To determine the effect of LCAT deficiency on macrophage RCT, LCAT(-/-) and LCAT(+/

199 secretion of PAF-AH followed by elevation of LCAT and PAF-AH levels in plasma.

200 cy patients will permit future evaluation of LCAT gene transfer as a possible treatment for glomerulo

201 ombinant LCAT were examined as a function of LCAT concentration.

202 This suggested that lack of LCAT enzyme did not explain the low CER in apoA-I(-)(/)(

203 The levels of LCAT in bile were low and declined to nearly undetectabl

204 oxide associated quantitatively with loss of LCAT activity in both discoidal HDL and HDL(3), the enzy

205 idation by MPO could account for the loss of LCAT activity.

206 to obtain accurate and robust measurement of LCAT esterification activity.

207 at have major implications for mechanisms of LCAT activation.

208 In addition, three mutants of LCAT (T123I, N228K, and (Delta53-71) were examined in th

209 ce by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HD

210 Also, the region of LCAT between residues 53 and 71 is essential for interfa

211 lopmental origin and the mechanistic role of LCAT deficiency.

212 METHODS AND The role of LCAT in RCT from macrophages was quantified with a valid

213 We further showed complementary roles of LCAT deficiency and cellular cholesterol reduction in th

214 Sequencing of LCAT cDNA clones demonstrated the coexistence of two mRN

215 a suggest a model wherein the active site of LCAT is shielded from soluble substrates by a dynamic li

216 e A2-like and esterification active sites of LCAT, respectively.

217 n the activity and fatty acid specificity of LCAT in vitro.

218 t the activity and fatty acid specificity of LCAT may be altered during the inflammatory response.

219 uman LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to

220 Here, we report the crystal structure of LCAT with an extended lid that blocks access to the acti

221 A subset of LCAT-KO mice accumulated lipoprotein X and developed pro

222 tein, both of which promoted the transfer of LCAT-derived high-density lipoprotein cholesterol ester

223 at macrophage RCT may not be as dependent on LCAT activity as has previously been believed.

224 e esterase inhibitor, which had no effect on LCAT at this concentration.

225 apoA-I of nascent HDL essential for optimal LCAT binding and catalytic efficiency.

226 apparent V(max) but not to apparent K(m) or LCAT binding to the PC surface.

227 s secreted by the parasite, but unlike other LCAT enzymes it is cleaved into two proteolytic fragment

228 Parasites overexpressing LCAT show increased virulence and faster egress.

229 Plasma LCAT activity was significantly increased after 5 hours

230 Plasma LCAT concentrations were dose-proportional, increased ra

231 LCAT specific activity increased, and plasma LCAT protein levels unchanged in apoE(-/-)/CBS(-/-) mice

232 nstrates a strong correlation between plasma LCAT activity and LCAT content.

233 us monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high d

234 accompanied by near normalizations of plasma LCAT, hepatic SRB-1, and LDL receptor and a significant

235 Mabs that recognize the putative LCAT activation site, residues 95-122, had normal reacti

236 Raising LCAT may be beneficial for CHD, as well as for familial

237 of total) than they were transferred by rat LCAT (0-21%).

238 With sn-2-18:0 PCs, however, rat LCAT exhibited greater alteration in positional specific

239 irst experiment, the reverse mutation in rat LCAT (rA149E) converted substrate specificity of rat LCA

240 149E) converted substrate specificity of rat LCAT toward that of the human enzyme, demonstrating that

241 substrate specificity similar to that of rat LCAT.

242 he hE149A construct was >1.7, similar to rat LCAT, whereas the triple mutation construct retained a r

243 for cholesteryl ester synthesis, whereas rat LCAT (which is 92% similar in amino acid sequence) prefe

244 various chain lengths at sn-1, human and rat LCATs derived, respectively, 5-72% and 1-20% of the tota

245 Both human and rat LCATs transferred exclusively the sn-2-acyl group from a

246 effect of LCAT deficiency on macrophage RCT, LCAT(-/-) and LCAT(+/-) mice were compared with wild-typ

247 and the binding kinetics of pure recombinant LCAT were examined as a function of LCAT concentration.

248 atients confirms previous reports of reduced LCAT activity in SCD and demonstrates a strong correlati

249 48, resides near the center of the protein's LCAT activation domain, we determined whether its oxidat

250 Selective LCAT-mediated reactivity with pre-beta(1)-HDL represents

251 These results suggest LCAT along with ACAT1/ACAT2 contribute to control pregne

252 We conclude that LCAT deficiency in LDLr-/- and apoE-/- mice fed an ather

253 These studies demonstrate that LCAT deficiency, similar to apoA-I deficiency, is associ

254 These results demonstrate that LCAT overexpression does not promote an increased rate o

255 dation, we investigated the possibility that LCAT may also hydrolyze polar PCs to lyso-PC during the

256 Results showed that LCAT activation was largely influenced by both rHDL part

257 This suggests that LCAT binding to the hybrid particles is sterically hinde

258 The LCAT activation capacity of apoA-I in vitro was nearly a

259 The LCAT structure suggests the molecular basis underlying h

260 The LCAT treatment caused only a small increase in HDL chole

261 substrate in the absence of SM activated the LCAT reaction only modestly, its co-incorporation with S

262 osterol (DHE) in place of cholesterol as the LCAT substrate.

263 For the LCAT mutants, the Delta53-71 (lid-deletion mutant) exhib

264 In the LCAT-/- LDLr-/- mice, TPC and atherosclerosis were signi

265 The HDL in the LCAT-deficient mice was reduced in its plasma concentrat

266 with a significant 2.7-fold increase in the LCAT-derived cholesteryl linoleate content found primari

267 phosphate, on the other hand, inhibited the LCAT reaction more strongly than SM.

268 with age-matched wild-type littermates, the LCAT activity in heterozygous and homozygous knockout mi

269 Sequencing of intron 5 of the LCAT locus in several primates revealed a G-->A transiti

270 ts apoA-I's central loop, which overlaps the LCAT activation domain.

271 idal into spherical HDL, indicating that the LCAT activity was rate-limiting for the biogenesis of HD

272 ge (HDX) mass spectrometry revealed that the LCAT lid is extremely dynamic in solution.

273 ural and functional defects that lead to the LCAT deficiency phenotypes of these mutations.

274 tant) exhibited no binding to LDL, while the LCAT-deficiency mutants (T123I and N228K) had nearly nor

275 Analysis of this LCAT-transgenic mouse model provides in vivo evidence fo

276 Thus, LCAT was able to efficiently esterify both cholesterol a

277 atients with hypoalphalipoproteinemia due to LCAT deficiency and (ii) a potential etiological role fo

278 lasma lecithin-cholesterol acyl transferase (LCAT) activity which probably accounted for the low cont

279 ilial lecithin cholesterol acyl transferase (LCAT) deficiency, we generated LCAT knockout (KO) mice a

280 nzyme lecithin-cholesterol acyl transferase (LCAT), which is critical for HDL maturation.

281 se in lecithin cholesterol acyl-transferase (LCAT) enzyme level and increased receptor mediated catab

282 nal development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary synd

283 Two LCAT glycosylation-deficient mutants, N84Q and N384Q, we

284 2-fold lower than the affinity of wild type LCAT (Kd = 2.3 x 10(-7) M).

285 the pure enzyme forms showed that wild type LCAT and both mutants were reactive with the water-solub

286 levels of glycosylation similar to wild type LCAT.

287 For the wild-type LCAT, binding to all lipid surfaces had the same associa

288 lly more enzymatically active than wild-type LCAT, but gradually lost activity within months; however

289 be significantly less stable than wild-type LCAT.

290 ontent of N84Q LCAT, compared with wild-type LCAT.

291 Es) to apoB-containing lipoproteins, whereas LCAT is an antiatherogenic enzyme that facilitates rever

292 +/- 2.0 micrometer(2) x 10(3)) compared with LCAT-Tg mice (35.7 +/- 2.0 micrometer(2) x 10(3); p < 0.

293 poA-II can modulate the reaction of HDL with LCAT by decreasing LCAT binding to hybrid particles and

294 wed that the reaction of the hybrid HDL with LCAT was inhibited 2-5-fold, relative to apoA-I-rHDL, du

295 re loops, proposed sites of interaction with LCAT (lecithin cholesteryl acyltransferase).

296 of apoAI, which enables the interaction with LCAT and subsequent maturation.

297 uced (-35% to -99%) in all mouse models with LCAT deficiency.

298 Patients with LCAT deficiency have abnormal small discoidal LDLs and H

299 h defects can be corrected by treatment with LCAT.

300 paring adipogenicity of Ldlr(+/+)xLcat(-/-) (LCAT-KO) SC with DKO SC identified a role for LCAT defic