Increase or decrease of HDL-cholesterol concentrations during pravastatin treatment depending on the pre-treatment HDL cholesterol levels

Narita, Yuichi; Kitazoe, Yasuhiro; Kurihara, Yukio; Okuhara, Yoshiyasu; Takamatsu, Kazunaga; Sakai, Noboru; Doi, Yoshinori

doi:10.1007/s002280050319

Cited by 9 publications

(1 citation statement)

References 7 publications

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“…In contrast, TAK‐475 did not affect plasma HDL cholesterol in beagle dogs (Table 1). In studies using patients with a relatively high HDL cholesterol level, HMG‐CoA reductase inhibitors have been reported as reducing or tending to reduce HDL cholesterol, although in patients with a low HDL cholesterol level some HMG‐CoA reductase inhibitors increase the level of this lipoprotein (Miserez et al ., 1994; Narita et al ., 1997).…”

Section: Discussionmentioning

confidence: 99%

Lipid‐lowering properties of TAK‐475, a squalene synthase inhibitor, in vivo and in vitro

Nishimoto

Amano

Tozawa

et al. 2003

British J Pharmacology

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1 Squalene synthase is the enzyme that converts farnesyl pyrophosphate to squalene in the cholesterol biosynthesis pathway. We examined the lipid-lowering properties of 1-[[(3R,5S)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidine-4-acetic acid (TAK-475), a novel squalene synthase inhibitor. 2 TAK-475 inhibited hepatic cholesterol biosynthesis in rats (ED 50 , 2.9 mg kg À1 ) and showed lipidlowering effects in beagle dogs, marmosets, cynomolgus monkeys and Wistar fatty rats. 3 In marmosets, TAK-475 (30, 100 mg kg À1 , p.o., for 4 days) lowered both plasma non-high-density lipoprotein (HDL) cholesterol and triglyceride, but did not affect plasma HDL cholesterol. On the other hand, atorvastatin (10, 30 mg kg À1 , p.o., for 4 days) lowered the levels of all these lipids. A correlation between decrease in triglyceride and increase in HDL cholesterol was observed, and TAK-475 increased HDL cholesterol with a smaller decrease in triglyceride than did atorvastatin. 4 TAK-475 (60 mg kg À1 , p.o., for 15 days) suppressed the rate of triglyceride secretion from the liver in hypertriglyceridemic Wistar fatty rats, which show an enhanced triglyceride secretion rate from the liver compared with their lean littermates. 5 In HepG2 cells, TAK-475 and its pharmacologically active metabolite, T-91485, increased the binding of 125 I-low-density lipoprotein (LDL) to LDL receptors. 6 These results suggest that TAK-475 has clear hypolipidemic effects in animals via inhibition of hepatic triglyceride secretion and upregulation of LDL receptors, and that TAK-475 might increase HDL cholesterol by decreasing triglyceride. Thus, TAK-475 is expected to be useful for the treatment of dyslipidemia.

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Section: Discussionmentioning

confidence: 99%

Lipid‐lowering properties of TAK‐475, a squalene synthase inhibitor, in vivo and in vitro

Nishimoto

Amano

Tozawa

et al. 2003

British J Pharmacology

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Pravastatin inhibits tumor growth through elevating the levels of apolipoprotein A1

Yeh

Cheng

Lin

et al. 2015

Adv in Digestive Medicine

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SummaryBackgroundStatins are a class of drugs used to lower cholesterol levels, accompanying increased high‐density lipoprotein (HDL) levels. Previous studies have suggested that statins can inhibit inflammation, and also reduce tumor proliferation. We therefore hypothesized that pravastatin, a member of the statins, mediating the inhibitory functions in tumor growth may be associated with the upregulated HDL constituent, apolipoprotein A1 (ApoA1).MethodsPravastatin‐induced inhibition in tumor proliferation in vitro and in xenografts was investigated. Reduced ApoA1 expressions were detected in the tumor regions in specimens from tumor patients as well in xenografts using Western Blotting. Moreover, ApoA1 was administered to inhibit tumor proliferation, and pravastatin was given to enhance the chemotherapeutic efficacy of doxorubicin (DOX).ResultsWe found a significant statistical reduction of ApoA1 in the tumor regions of specimens from gastric cancer and colorectal cancer patients. MKN45 cells proliferation was inhibited by 18% under the growing medium containing pravastatin. ApoA1 levels were elevated in liver Clone 9 cells administered pravastatin, but not in MKN45 cells. In vitro studies revealed that ApoA1 can reduce MKN45 tumor proliferation. Moreover, the tumor volume was significantly reduced in in vivo xenografts after the administration of pravastatin. Combined treatments of pravastatin with DOX significantly minimized the size of tumors, leading to a better therapeutic efficacy.ConclusionThis study demonstrated that pravastatin elevated ApoA1, an HDL major constituent with anti‐inflammatory characteristics, which displayed strong adversary associations with tumor developments and growth. Increasing the amounts of ApoA1 by pravastatin coupled with DOX may improve the therapeutic efficacy for cancer treatment.

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Effects of ABCA1 SNPs, including the C-105T novel variant, on serum lipids of Brazilian individuals

Genvigir

Soares

Hirata

et al. 2008

Clinica Chimica Acta

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Increase or decrease of HDL-cholesterol concentrations during pravastatin treatment depending on the pre-treatment HDL cholesterol levels

Cited by 9 publications

References 7 publications

Lipid‐lowering properties of TAK‐475, a squalene synthase inhibitor, in vivo and in vitro

Lipid‐lowering properties of TAK‐475, a squalene synthase inhibitor, in vivo and in vitro

Pravastatin inhibits tumor growth through elevating the levels of apolipoprotein A1

Effects of ABCA1 SNPs, including the C-105T novel variant, on serum lipids of Brazilian individuals

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