Evaluation of apolipoprotein B-100 fragmentation and cross-linkage in serum as an index of atherosclerosis

Hashimoto, Ryuji; Matsukawa, N.; Nariyama, Yoko; Ogiri, Yukako; Hamagawa, Eri; Tanaka, Kyoko; Usui, Y; Nakano, Soichiro; Maruyama, Taro; Kyotani, S.; Tsushima, Motoo; Kojo, Shosuke

doi:10.1016/s1388-1981(02)00299-8

Cited by 12 publications

(17 citation statements)

References 41 publications

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“…In addition, the fragmentation and cross-link pattern of apoB positively correlated with age, IMT, and LDL cholesterol, and negatively correlated with HDL cholesterol, thus being a good index for atherosclerosis. 21 The present study demonstrated that typical oxidation of LDL with Cu 2+ caused a decrease in a-tocopherol in the lag phase, followed by an increase in the absorption at 234 nm 4 and simultaneous reductions in apoB, with a molecular mass of 512 kDa and particle size of LDL (Fig. 1).…”

Section: Discussionsupporting

confidence: 62%

Decrease in the particle size of low-density lipoprotein (LDL) by oxidation

Hidaka

Inoue

Kutsukake

et al. 2005

Bioorganic & Medicinal Chemistry Letters

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Section: Discussionsupporting

confidence: 62%

Decrease in the particle size of low-density lipoprotein (LDL) by oxidation

Hidaka

Inoue

Kutsukake

et al. 2005

Bioorganic & Medicinal Chemistry Letters

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“…For electrophoresis, 15 µL of the sample was applied to SDS gel electrophoresis on a 4% polyacrylamide slab gel (1 mm thick) as described (22,29). Immunoblot analysis was performed as previously described previously (21)(22)(23). Proteins separated on the gel were eletrophoretically transferred to PVDF membrane filters and immunoblotting analyses of apoB were performed as previously described (23).…”

Section: Methodsmentioning

confidence: 99%

“…Among plasma proteins, apoB is unusually reactive to radical reactions compared to albumin and transferrin (21), and its reactivity is even comparable to α-tocopherol (21). In normal human serum, both fragmented and cross-linked apoB proteins are present and these oxidation reaction products of LDL tend to increase with age (23). In addition, we reported that B-ox, namely the sum of fragmented and conjugated apoB proteins determined by an immunoblot assay, showed a significant positive correlation with intima-media thickness of the carotid artery (IMT) and LDL cholesterol, and a negative correlation with HDL cholesterol and plasma vitamin C, which was an outstanding antioxidant in plasma (23,24).…”

mentioning

confidence: 99%

Association of ceramides in human plasma with risk factors of atherosclerosis

Ichi

Nakahara

Miyashita

et al. 2006

Lipids

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Atherosclerosis is a multifactorial disorder. Recent studies indicate that the plasma level of sphingomyelin, which yields ceramide, correlates with the risk of coronary heart disease. Therefore, ceramide, a well-known lipid causing apoptosis in various cell types, may contribute to atherogenesis. We examined the relationship between ceramide concentration and risk factors of atherosclerosis in normal human plasma using electrospray tandem mass spectrometry (LC-MS/MS). Major ceramides in human plasma were C24:0 and C24:1. The ceramide concentration showed a significant positive correlation with total cholesterol (TC) and triglycerides (TG). In addition, plasma ceramide level increased drastically at a high level of LDL cholesterol (more than 170 mg/dL). Our previous studies demonstrated that the sum of fragmented and conjugated apolipoprotein B-100 proteins (B-ox), which were products of a radical reaction of LDL as well as plasma, was a reliable index of atherosclerosis. B-ox showed a significant positive correlation with the plasma ceramide level. Based on these results, we propose that the ceramide level in human plasma is a risk factor at the early stages of atherosclerosis.

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“…In addition, lipid peroxidation products could modify apoB. 24) Because fraxetin shows the most potent anti-oxidation ability, we then assessed its inhibitory effect against apoB fragmentation. Fraxetin (0.2-10 mM), concentration-dependently inhibited apoB fragmentation after Cu 2ϩ -induced LDL oxidation (Fig.…”

Section: ؉mentioning

confidence: 99%

Dual Anti-oxidative Effects of Fraxetin Isolated from Fraxinus rhinchophylla

Thương

Pokharel

Lee

et al. 2009

Biological & Pharmaceutical Bulletin

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Atherosclerosis is main cause of arteriosclerosis. The pivotal role of low-density lipoprotein (LDL) oxidation in atherogenesis suggests antioxidants may help prevent cardiovascular disease. Fraxinus rhynchophylla DENCE (Oleaceae) is a traditional medicinal plant from East Asia. During the course of characterizing potential drug candidates from natural products, we isolated two major coumarins, esculetin and fraxetin and found that fraxetin has dual-antioxidative functions. Low concentrations (1-5 m mM) of fraxetin potently inhibited LDL oxidation induced by metal and free radicals. Moreover, treatment of vascular smooth muscle cells (VSMCs) with higher concentrations (above 30 m mM) of fraxetin significantly increased the protein level of heme oxygenase-1 (HO-1), a key enzyme that inhibits vascular proliferation and atherosclerosis. Subcellular fractionation and reporter gene analysis using an antioxidant response element (ARE) construct revealed that fraxetin increased the level of nuclear factor (NF)-E2-related factor 2 (Nrf2) and reporter activity, and these were associated with the induction of antioxidant enzymes, such as HO-1 and glutathione S-transferase-a a. In conclusion, fraxetin has direct protective properties against LDL oxidation at lower concentrations, and higher concentrations of fraxetin induce antioxidant enzymes via Nrf2/ARE activation. These effects suggest potential anti-atherosclerosis effects of Fraxinus rhynchophylla D.

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Evaluation of apolipoprotein B-100 fragmentation and cross-linkage in serum as an index of atherosclerosis

Cited by 12 publications

References 41 publications

Decrease in the particle size of low-density lipoprotein (LDL) by oxidation

Decrease in the particle size of low-density lipoprotein (LDL) by oxidation

Association of ceramides in human plasma with risk factors of atherosclerosis

Dual Anti-oxidative Effects of Fraxetin Isolated from Fraxinus rhinchophylla

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