Abstract
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. 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 chro-matography (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. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 643-656 |
| Number of pages | 14 |
| Journal | Journal of atherosclerosis and thrombosis |
| Volume | 19 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 07-08-2012 |
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All Science Journal Classification (ASJC) codes
- Internal Medicine
- Cardiology and Cardiovascular Medicine
- Biochemistry, medical
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Effect of Probucol on Antioxidant Properties of HDL in Patients with Heterozygous Familial Hypercholesterolemia. / Inagaki, Miwako; Nakagawa-Toyama, Yumiko; Nishida, Makoto; Nakatani, Kazuhiro; Nakaoka, Hajime; Kawase, Miyako; Kawase, Ryota; Tsubakio-Yamamoto, Kazumi; Masuda, Daisaku; Ohama, Tohru; Matsuyama, Akifumi; Ishigami, Masato; Komuro, Issei; Yamashita, Shizuya.
In: Journal of atherosclerosis and thrombosis, Vol. 19, No. 7, 07.08.2012, p. 643-656.Research output: Contribution to journal › Article
TY - JOUR
T1 - Effect of Probucol on Antioxidant Properties of HDL in Patients with Heterozygous Familial Hypercholesterolemia
AU - Inagaki, Miwako
AU - Nakagawa-Toyama, Yumiko
AU - Nishida, Makoto
AU - Nakatani, Kazuhiro
AU - Nakaoka, Hajime
AU - Kawase, Miyako
AU - Kawase, Ryota
AU - Tsubakio-Yamamoto, Kazumi
AU - Masuda, Daisaku
AU - Ohama, Tohru
AU - Matsuyama, Akifumi
AU - Ishigami, Masato
AU - Komuro, Issei
AU - Yamashita, Shizuya
PY - 2012/8/7
Y1 - 2012/8/7
N2 - 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. 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 chro-matography (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. 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.
AB - 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. 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 chro-matography (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. 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84864510599&partnerID=8YFLogxK
U2 - 10.5551/jat.12807
DO - 10.5551/jat.12807
M3 - Article
C2 - 22785024
AN - SCOPUS:84864510599
VL - 19
SP - 643
EP - 656
JO - Journal of Atherosclerosis and Thrombosis
JF - Journal of Atherosclerosis and Thrombosis
SN - 1340-3478
IS - 7
ER -