PMID- 9258412
OWN - NLM
STAT- MEDLINE
DCOM- 19971014
LR  - 20190718
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 133
IP  - 1
DP  - 1997 Aug
TI  - ACAT inhibitor HL-004 accelerates the regression of hypercholesterolemia in 
      stroke-prone spontaneously hypertensive rats (SHRSP): stimulation of bile acid 
      production by HL-004.
PG  - 97-104
AB  - The effect of the acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor HL-004 on 
      bile acid production was studied during the regression phase of pre-established 
      hypercholesterolemia in stroke-prone spontaneously hypertensive rats (SHRSP). 
      These rats were fed a hypercholesterolemic diet containing 5% cholesterol, 2% 
      cholic acid, and 20% suet for 30 days to induce hypercholesterolemia. The 
      regression phase was started by switching the diet to normal chow, followed by 
      another 30 days of the diet. The decrease in serum cholesterol level was 
      accelerated by treatment with 0.09% HL-004. At the end of regression, hepatic 
      ACAT activity was significantly lower in the HL-004 treated animals, an event 
      concomitant with the significant decrease in cholesteryl ester content in the 
      liver. In contrast hepatic cholesterol 7 alpha-hydroxylase activity was 
      maintained at a higher level in the HL-004 treated animals. HL-004 increased the 
      secretion of bile acid and biliary lipids in bile duct-cannulated SHRSP. In 
      HepG2:cells, HL-004 at 1-30 microM dose-dependently stimulated bile acid 
      synthesis from [3H]cholesterol. When cholesterol 7 alpha-hydroxylase activity of 
      the liver was compared ex vivo in the presence and in the absence of exogenous 
      cholesterol, it was suggested that the higher 7 alpha-hydroxylase activity of the 
      HL-004 group could be attributed not only to expansion of the endogenous 
      cholesterol pool, which may be the result of hepatic ACAT inhibition by HL-004 
      but to the direct effect of HL-004 on bile acid production. Thus, HL-004 
      accelerates the regression of hypercholesterolemia, an event which may be related 
      to the stimulation of bile acid production in the liver.
FAU - Murakami, S
AU  - Murakami S
AD  - Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd., Ohmiya, Japan. 
      s12867@ccm.taisho.co.jp
FAU - Yamagishi, I
AU  - Yamagishi I
FAU - Sato, M
AU  - Sato M
FAU - Tomisawa, K
AU  - Tomisawa K
FAU - Nara, Y
AU  - Nara Y
FAU - Yamori, Y
AU  - Yamori Y
LA  - eng
PT  - Journal Article
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Acetanilides)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (HL 004)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.3.1.26 (Sterol O-Acyltransferase)
SB  - IM
MH  - Acetanilides/*pharmacology
MH  - Animals
MH  - Anticholesteremic Agents/*pharmacology
MH  - Bile Acids and Salts/*biosynthesis
MH  - Cerebrovascular Disorders/etiology
MH  - Cholesterol/blood
MH  - Cholesterol, HDL/blood
MH  - Enzyme Inhibitors/*pharmacology
MH  - Hypercholesterolemia/*drug therapy
MH  - Liver/metabolism
MH  - Male
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Sterol O-Acyltransferase/*antagonists & inhibitors
EDAT- 1997/08/01 00:00
MHDA- 1997/08/01 00:01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1997/08/01 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
AID - S0021-9150(97)00121-4 [pii]
AID - 10.1016/s0021-9150(97)00121-4 [doi]
PST - ppublish
SO  - Atherosclerosis. 1997 Aug;133(1):97-104. doi: 10.1016/s0021-9150(97)00121-4.