Molecular Mechanisms of Cholesteryl Ester Transfer Protein Deficiency in Japanese

Nagano, Makoto; Yamashita, Shizuya; Hirano, Ken‐ichi; Takano, Mayumi; Maruyama, Takao; Ishihara, Misa; Sagehashi, Yukiko; Kujiraoka, Takeshi; Tanaka, Katsu; Hashimoto, Hiroaki; Sakai, Naohiko; Nakajima, Noriaki; Egashira, Tohru; Matsuzawa, Yūji

doi:10.5551/jat.11.110

Cited by 99 publications

(86 citation statements)

References 64 publications

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“…Esterification of free cholesterol by LCAT contributes to HDL maturation. Subsequently, CETP action enables the transfer of cholesteryl ester from HDL to lipoproteins of lower density, making HDL particles cholesteryl ester-depleted and triglyceride-enriched 17,18) . Epidemiological studies have indicated an inverse relationship between the HDL-C level and cardiovascular disease [19][20][21][22] .…”

Section: Discussionmentioning

confidence: 99%

HMG-CoA Reductase Inhibitor, Simvastatin Improves Reverse Cholesterol Transport in Type 2 Diabetic Patients with Hyperlipidemia

Guan

Tamasawa

Murakami

et al. 2008

JAT

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Aim: ApoA-and HDL promote cellular cholesterol efflux in the early stages of the reverse cholesterol transport (RCT) pathway. A low plasma HDL-C level is characteristic of atherogenic dyslipidemia in patients with type 2 diabetes. We evaluated plasma lipid levels and the expression of factors related to RCT in type 2 diabetic patients, and the effects of an HMG-CoA reductase inhibitor, simvastatin, were studied. Methods: Messenger RNA (mRNA) expression in circulating mononuclear cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), focusing on the following factors: liver X receptor (LXR ), ATP-binding cassette A1 (ABCA1), scavenger receptor class B type 1 (SR-B1), apolipoprotein E (ApoE), apolipoprotein A-1 (ApoA-1), caveolin, and cholesterol ester transfer protein (CETP). Type 2 diabetic subjects (n 29) were divided into three subgroups: patients with normolipidemia (DM group, n 11), patients with untreated hyperlipidemia (DMHL group, n 10), and those with hyperlipidemia treated with simvastatin 5-10 mg/day (DMST group, n 8). The control group (CNT group) included seven healthy volunteers. Results: Simvastatin treatment significantly increased plasma levels of ApoA-compared to the other three groups. Simvastatin treatment improved the expression of mRNA for LXR , ABCA1, and ApoA-compared with DMHL or control groups. Conclusion: Our data suggest that RCT may be reduced in type 2 diabetic patients with hyperlipidemia, and simvastatin may be able to improve reverse cholesterol transport for this population of diabetic patients. J Atheroscler

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Section: Discussionmentioning

confidence: 99%

HMG-CoA Reductase Inhibitor, Simvastatin Improves Reverse Cholesterol Transport in Type 2 Diabetic Patients with Hyperlipidemia

Guan

Tamasawa

Murakami

et al. 2008

JAT

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“…Thus, CETP plays an important role in the reverse cholesterol transport pathway, as changes in CETP activity are inversely correlated with plasma HDL-C concentrations [6]. CETP inhibitors significantly raise plasma HDL-C concentration; however, clinical trials of one CETP inhibitor, torcetrapib, have been discontinued due in part to the lack of atheroprotective effects.…”

Section: Introductionmentioning

confidence: 99%

Cholesteryl ester transfer protein genetic polymorphisms, HDL cholesterol, and subclinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

et al. 2008

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The cholesteryl ester transport protein (CETP) plays a key role in high-density lipoprotein (HDL) metabolism. Genetic variants that alter CETP activity and concentration may cause significant alterations in HDL-cholesterol (HDL-C) concentration; however, controversies remain about whether these genetic variants are associated with atherosclerosis. We genotyped the CETP R451Q, A373P, -629C/A, Taq1B, and -2505C/A polymorphisms in a cohort of Caucasian, Chinese, African-American, and Hispanic individuals within the Multi-Ethnic Study of Atherosclerosis. Genotypes were examined in relationship to HDL-C, CETP activity, CETP concentration, and three measures of subclinical cardiovascular disease (CVD): coronary artery calcium (CAC) measured by fast CT scanning, and carotid intimal-medial thickness (IMT) and carotid artery plaque, measured by ultrasonography. Carriers of the 451Q and 373P alleles have significantly higher CETP concentration (22.4% and 19.5%, respectively; p<0.001) and activity (13.1% and 9.4%, respectively; p<0.01) and lower HDL-C (5.6% and 6.0%, respectively; p<0.05). The minor alleles of the R451Q and A373P polymorphisms are associated with the presence of CAC, even after adjusting for CVD risk factors and HDL-C (p=0.006 and p=0.01, respectively). The R451Q polymorphism is also associated with presence of carotid artery plaque (p=0.036). Neither polymorphism is associated with common or internal carotid IMT. We confirmed that the -629A, Taq1B B2, and -2505A alleles are significantly associated with lower CETP concentration

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“…Furthermore, in the context of an aggressive LDL-C target for patients with CAD 24) , a U-shaped relationship between HDL-C and all-cause mortality has been recently shown, mortality being higher for patients with both low and very elevated HDL-C 35) . This relationship was initially described in Japanese patients, where marked hyperalphalipoproteinemia, associated with juvenile corneal opacification, is frequently caused by genetic CEPT deficiency [11][12][13] . Since CEPT is a key protein in reverse cholesterol transport, its deficiency could favor coronary atherosclerosis and increase cardiovascular risk 36) .…”

Section: Discussionmentioning

confidence: 99%

“…A significant U-shaped relationship between HDL-C levels and the incidence of ischemic changes in electrocardiograms has been shown in Japanese patients. In this population, marked hyperalphalipoproteinemia appears to be caused by genetic cholesteril ester transfer protein (CEPT) deficiency [11][12][13] . Mutations of the CEPT gene have also been documented in Italian subjects with hyperalphalipoproteinemia and in other populations 14,15) .…”

Section: Laboratory Testsmentioning

confidence: 99%

High Density Lipoprotein Cholesterol in Coronary Artery Disease: When Higher Means Later

Sbrana

Puntoni

Bigazzi

et al. 2013

JAT

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Aim: Although high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with cardiovascular risk, patients with elevated HDL-C also develop coronary artery disease (CAD) and cardiac events. We aimed to draw the clinical profile of CAD patients with elevated HDL-C and to assess the prognostic impact of elevated HDL-C. Methods: We prospectively examined 2322 patients (age 67±10 years, 79% male) with chronic CAD, defined by ＞50% coronary stenosis and/or previous myocardial infarction.

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Molecular Mechanisms of Cholesteryl Ester Transfer Protein Deficiency in Japanese

Abstract: Plasma cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to apolipoprotein

Cited by 99 publications

References 64 publications

HMG-CoA Reductase Inhibitor, Simvastatin Improves Reverse Cholesterol Transport in Type 2 Diabetic Patients with Hyperlipidemia

HMG-CoA Reductase Inhibitor, Simvastatin Improves Reverse Cholesterol Transport in Type 2 Diabetic Patients with Hyperlipidemia

Cholesteryl ester transfer protein genetic polymorphisms, HDL cholesterol, and subclinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

High Density Lipoprotein Cholesterol in Coronary Artery Disease: When Higher Means Later

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