Effect of Probucol on Antioxidant Properties of HDL in Patients with Heterozygous Familial Hypercholesterolemia
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- Inagaki Miwako
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
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- Nakagawa-Toyama Yumiko
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Health Care Center, Osaka University. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Health Care Center, Osaka University.
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- Nishida Makoto
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Health Care Center, Osaka University. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Health Care Center, Osaka University.
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- Nakatani Kazuhiro
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
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- Nakaoka Hajime
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
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- Kawase Miyako
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
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- Kawase Ryota
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
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- Tsubakio-Yamamoto Kazumi
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
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- Masuda Daisaku
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
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- Ohama Tohru
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Health Care Center, Osaka University. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
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- Matsuyama Akifumi
- Department of Somatic Stem Cell Therapy and Health Policy, Foundation for Biomedical Research and Innovation. Department of Somatic Stem Cell Therapy and Health Policy, Foundation for Biomedical Research and Innovation.
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- Ishigami Masato
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine
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- Komuro Issei
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
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- Yamashita Shizuya
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
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Aim: High density lipoprotein (HDL) has multi-antiatherogenic effects such as antioxidation and anti-inflammation, in addition to being a key mediator of reverse cholesterol transport. Probucol, known as a lipid lowering drug, is also a potent antioxidant, but it decreases serum HDL cholesterol (HDL-C) levels. To elucidate the effect of probucol on antioxidant properties of HDL, we investigated the function of HDL derived from patients with heterozygous familial hypercholesterolemia (FH) who have been treated with probucol.<BR>Methods and Results: Probucol-treated FH patients (n=21) showed a 47% reduction of serum HDL-C levels compared to probucol-untreated FH patients (n=15). High performance liquid chromatography (HPLC) analysis revealed that probucol diminished HDL particle size compared to the non-treated group. Antioxidant capacity of HDL was evaluated by its effect to protect reference LDL from oxidation induced in the presence of an oxidizing agent, AAPH. The HDL derived from the probucol-treated group demonstrated a significantly prolonged time to start oxidation by 112%, decreased the maximum oxidation rate by 14%, and lowered the maximum concentration of conjugated dienes formation by 15%. Furthermore, HDL-associated paraoxonase 1 (PON1) activity, but not platelet-activating factor acetyl-hydrolase (PAF-AH) correlated with these measurements of HDL anti-oxidative activity. Treatment with probucol in vitro and inhibition of PON1 activity demonstrated that probucol in HDL particles and increase of PON1 activity might largely contribute to the increase of HDL anti-oxidative activity.<BR>Conclusion: Probucol reduced HDL-C levels and HDL particle size in patients with heterozygous FH, while it concomitantly enhanced HDL anti-oxidative properties, possibly through increasing PON1 activity.
収録刊行物
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- Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ
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Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ 19 (7), 643-656, 2012
一般社団法人 日本動脈硬化学会