Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice

Choi, Jaehoon; Jeon, Hyung Jun; Park, Jong‐Gil; Sonn, Seong Keun; Lee, Mi Ran; Lee, Mi-Ni; You, Hye Jin; Kim, Geunyoung; Kim, Jae Hong; Lee, Mun Han; Kwon, Oh‐Seung; Nam, Ki-Hoan; Kim, Hyoung-Chin; Jeong, Tae‐Sook; Lee, Woo Song; Oh, Goo Taeg

doi:10.1016/j.atherosclerosis.2010.05.003

Cited by 15 publications

(8 citation statements)

References 23 publications

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“…Evidence suggests that the rare T allele of rs17525495 increases LTA4H gene transcription [37], while the rare alleles of rs6538697, rs2660898, and rs1978331 are associated with lower LTB4 levels [13], which is comparable to the present study findings. Some studies have shown that LTB4 biosynthesis is regulated by cholesterol [38], and inhibition of Leukotriene may reduce plasma TG levels [39]. Our data also showed high correlation of LTB4 levels with TC, TG, and LDL-cholesterol, after adjusting for age, gender, and statins.…”

Section: Discussionsupporting

confidence: 69%

Association of Leukotriene Gene Variants and Plasma LTB4 Levels with Coronary Artery Disease in Asian Indians

Nair

Shanker

Arvind

et al. 2013

ISRN Vascular Medicine

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Leukotrienes are potent inflammatory and lipid mediators that participate in atherosclerosis. We analyzed the association of Leukotriene gene (ALOX5, ALOX5AP, LTA4H, and LTC4S) polymorphisms and plasma Leukotriene B4 (LTB4) levels with coronary artery disease (CAD) in a representative cohort of Asian Indians. In all, 136 functional single nucleotide polymorphisms (SNPs) were selected using in silico tools. Forty-five polymorphic SNPs were ranked for predicted functional effect using FastSNP. Finally, 14 functional SNPs along with 10 SNPs identified from the literature were genotyped in 340 CAD patients and 340 controls. Plasma LTB4 levels were measured in 150 cases and 150 controls. None of the 24 SNPs showed significant association with CAD. Plasma LTB4 levels were higher in cases than in controls (76.42 ± 4.46 pg/mL versus 60.89 ± 2.61 pg/mL) ( = 0.003), with greater risk being associated with the top quartile as compared to the bottom quartile after adjusting for potential confounders (OR 8.94, 95% CI 2.56-31.95; = 0.001). Four SNPs in the LTA4H gene showed significant association with LTB4 levels ( < 0.05) of which rs1978331 ( = 0.035) remained significant after correction for multiple testing. LTB4 showed strong correlation with lipids ( = 0.24-34) only in cases. Our pilot study suggests that the association between Leukotrienes gene polymorphisms and CAD risk may be modulated through plasma LTB4 levels.

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Section: Discussionsupporting

confidence: 69%

Association of Leukotriene Gene Variants and Plasma LTB4 Levels with Coronary Artery Disease in Asian Indians

Nair

Shanker

Arvind

et al. 2013

ISRN Vascular Medicine

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“…This suggests that factors in addition to plasma lipids might contribute to athero-protection. The finding that high plasma cholesterol levels do not always correlate with lesion area has been demonstrated by others 20, 21 . Our earlier studies 22 have suggested that oxidized linoleic acid together with a high fat diet contributes to an increase in lesions despite comparable plasma lipids.…”

Section: Discussionmentioning

confidence: 67%

Pretreatment with n-6 PUFA protects against subsequent high fat diet induced atherosclerosis—Potential role of oxidative stress-induced antioxidant defense

Penumetcha¹,

Song²,

Merchant³

et al. 2012

Atherosclerosis

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Objectives Recent evidence suggests that oxidative stress can promote antioxidant defense and thus be athero-protective. n-6 Polyunsaturated fatty acids (n-6 PUFA) are more prone to oxidation, compared to monounsaturated fatty acids (MUFA) and yet have proven anti-atherosclerotic effects. In this study, we tested whether early exposure to a diet rich in n-6 PUFA, compared to a MUFA rich diet would reduce lesion burden, even with subsequent exposure to a high fat, high cholesterol diet (HF). Further, we tested to determine whether oxidative mechanisms are involved in such protection. Methods and Results Twenty four, 4 week old, male, LDL receptor knockout (LDL-R−/−) mice were divided into two groups and fed either a n-6 PUFA rich or a MUFA rich diet for a period of 12 weeks. At this point, 4 mice from each group were euthanized and the remaining 8 mice from each group were fed a HF diet for four weeks. Atherosclerotic lesions, plasma lipids, autoantibodies to lipid peroxide modified proteins, isoprostanes and aortic catalase levels were measured. The n-6 PUFA diet reduced aortic lesions and plasma lipids compared to the MUFA diet and this reduction in lesions continued even after the mice were switched over to the HF diet, despite the fact that the plasma lipids were similar in both groups after the HF diet. n-6 PUFA fed mice had highest plasma isoprostane levels, indicating oxidative stress, but also had higher levels of aortic catalase. On the other hand, MUFA fed mice had comparatively lower levels of isoprostanes and their aortic catalase levels remained low. Finally, aortic lesions were negatively correlated with isoprostanes and catalase. Conclusion An initial exposure to a n-6 PUFA rich diet compared to a MUFA rich diet reduces atherosclerotic lesions and this protection probably involves oxidative stress induced by PUFA.

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“…Recently, we reported that the benzylidenethiazole analog BHB-TZD is a dual inhibitor for cyclooxygenase and 5-lipoxygenase. BHB-TZD showed anti-atherogenic effects in hyperlipidemic mice by reducing macrophage infiltration into atherosclerotic lesions, thereby increasing plaque stability (28). Another benzylidenethiazole analog, HMB-TZD, inhibits 5-lipoxygenase, reduces cell migration and adhesion by decreasing proinflammatory molecule production, and ameliorates atherosclerotic lesion formation in LDL receptor-deficient mice (29).…”

Section: Figmentioning

confidence: 99%

The role of peroxidases in the pathogenesis of atherosclerosis

Park¹,

Oh²

2011

BMB Reports

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Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice

Cited by 15 publications

References 23 publications

Association of Leukotriene Gene Variants and Plasma LTB4 Levels with Coronary Artery Disease in Asian Indians

Association of Leukotriene Gene Variants and Plasma LTB4 Levels with Coronary Artery Disease in Asian Indians

Pretreatment with n-6 PUFA protects against subsequent high fat diet induced atherosclerosis—Potential role of oxidative stress-induced antioxidant defense

The role of peroxidases in the pathogenesis of atherosclerosis

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