High-density lipoprotein composition and development of coronary artery disease

• Project/Area Number: 23591334
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kanazawa University
• Principal Investigator: NOHARA Atsushi 金沢大学, 医薬保健学総合研究科, 特任准教授 (50313648)
• Co-Investigator(Renkei-kenkyūsha): KOBAYASHI Junji 金沢医科大学, 総合内科学, 教授 (60302577) ; INAZU Akihiro 金沢大学, 医薬保健学総合研究科, 教授 (80293348) ; YAGI Kunimasa 金沢大学, 医薬保健学総合研究科, 准教授 (30293343) ; NOGUCHI Tohru 金沢大学, 医薬保健学総合研究科, 特任助教 (40456421)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 高比重リポ蛋白 / リポ蛋白代謝 / コレステリルエステル転送蛋白 / 家族性高コレステロール血症 / 残余リスク / コレステロールエステル転送蛋白 / 胆汁酸受容体 / 脂質代謝異常

Research Abstract

Many studies suggest that high-density lipoprotein (HDL) composition may contribute to coronary atherosclerosis development rather than HDL-cholesterol. In this study, we demonstrated that increased HDL-TG/HDL-PL ratio was significantly associated with many cardiovascular risk factors. This index was strongly correlated with diabetes and chronic kidney disease, and may represent functional abnormalities of HDL.
Plasma cholesteryl-ester transfer protein (CETP) mass showed positive correlation with HDL-TG/HDL-PL ratio. HDL-TG/HDL-PL ratio was significantly lower in CETP deficiency, common genetic background in Japan.

Research Products

• [Journal Article] Nohara A, Kobayashi J , Kawashiri MA, Tada H, Inazu A, Jiang M, Mabuchi H, Bujo H. Clinical significance of measuring soluble LR11, a circulating marker of atherosclerosis and HbA1c in familial hypercholesterolemia (2014)
  • Author(s): Nohara A, Kobayashi J , Kawashiri MA, Tada H, Inazu A, Jiang M, Mabuchi H, Bujo H
  • Journal Title: Clinical Biochemistry Volume: 47 Issue: 13-14 Pages: 1326-1328
  • DOI: 10.1016/j.clinbiochem.2014.05.003
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of measuring soluble LR11, a circulating marker of atherosclerosis and HbA1c in familial hypercholesterolemia (2014)
  • Author(s): Nohara A, Kobayashi J, Kawashiri M-A, Tada H, Inazu A, Jiang M, Mabuchi H, Bujo H.
  • Journal Title: Clinical Biochemistry Volume: in press
  • Peer Reviewed
• [Journal Article] Impact of serum retinol-binding protein 4 levels on regulation of remnant-like particles triglyceride in type 2 diabetes mellitus (2013)
  • Author(s): Yamaaki N, Yagi K, Kobayashi J, Nohara A, Ito N, Asano A, Nakano K, Liu J, Okamoto T, Mori Y, Ohbatake A, Okazaki S, Takeda Y, Yamagishi M
  • Journal Title: J Diabetes Res Volume: 2013 Pages: 143515-143515
  • DOI: 10.1155/2013/143515
  • Peer Reviewed
• [Journal Article] MTP inhibitor for treating severe LDL cholesterolemia (2013)
  • Author(s): Mabuchi H, Nohara A
  • Journal Title: Clinical Lipidology Volume: 8(4) Pages: 387-389
  • URL: http://www.futuremedicine.com
  • Peer Reviewed
• [Journal Article] Effects of coenzyme Q(10) on LDL oxidation in vitro (2013)
  • Author(s): Ahmadvand H, Mabuchi H, Nohara A, Kobayahi J, Kawashiri MA
  • Journal Title: Acta Med Iran Volume: 51(1) Pages: 12-8
  • URL: http://acta.tums.ac.ir
  • Peer Reviewed
• [Journal Article] Post-prandial remnant lipoprotein metabolism in autosomal recessive hypercholesterolaemia (2012)
  • Author(s): Tada H
  • Journal Title: Eur J Clin Invest Volume: 42 Issue: 10 Pages: 1094-1099
  • DOI: 10.1111/j.1365-2362.2012.02700.x
  • Peer Reviewed
• [Journal Article] Altered metabolism of low-density lipoprotein and very-low-density lipoprotein remnant in autosomal recessive hypercholesterolemia : results from stable isotope kinetic study in vivo (2012)
  • Author(s): Tada H, Kawashiri MA, Ikewaki K, Terao Y, Noguchi T, Nakanishi C, Tsuchida M, Takata M, Miwa K, Konno T, Hayashi K, Nohara A, Inazu A, Kobayashi J, Mabuchi H, Yamagishi M
  • Journal Title: Circ Cardiovasc Genet Volume: 5 Issue: 1 Pages: 35-41
  • DOI: 10.1161/circgenetics.111.960948
  • Peer Reviewed
• [Journal Article] Novel mutations of cholesteryl ester transfer protein(CETP) gene in Japanese hyperalphalipoproteinemic subjects (2012)
  • Author(s): Ohtani R, Inazu A, Noji Y, Wakasugi T, Miwa K, Tada H, Kawashiri MA, Noguchi T, Nohara A, Kobayashi J, Koizumi J, Yamagishi M, Mabuchi H
  • Journal Title: Clin Chim Acta Volume: 413 Issue: 5-6 Pages: 537-43
  • DOI: 10.1016/j.cca.2011.11.010
  • NAID: 120004026116
  • Peer Reviewed
• [Journal Article] Efficacy and safety of coadministration of rosuvastatin, ezetimibe, and colestimide in heterozygous familial hypercholesterolemia (2012)
  • Author(s): Kawashiri MA, Nohara A, Noguchi T, Tada H, Nakanishi C, Mori M, Konno T, Hayashi K, Fujino N, Inazu A, Kobayashi J, Mabuchi H, Yamagishi M
  • Journal Title: Am J Cardiol Volume: 109 Issue: 3 Pages: 364-9
  • DOI: 10.1016/j.amjcard.2011.09.019
  • Peer Reviewed
• [Journal Article] A novel type of familial hypercholesterolemia : double heterozygous mutations in LDL receptor and LDL receptor adaptor protein 1 gene (2011)
  • Author(s): Tada H, Kawashiri MA, Ohtani R, Noguchi T, Nakanishi C, Konno T, Hayashi K, Nohara A, Inazu A, Kobayashi J, Mabuchi H, Yamagishi M
  • Journal Title: Atherosclerosis Volume: 219 Issue: 2 Pages: 663-6
  • DOI: 10.1016/j.atherosclerosis.2011.08.004
  • NAID: 120003368152
  • Peer Reviewed
• [Journal Article] Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus : results from a crossover study (2011)
  • Author(s): Noguchi T, et al., 計14名、9番目
  • Journal Title: Atherosclerosis Volume: 217 Issue: 1 Pages: 165-170
  • DOI: 10.1016/j.atherosclerosis.2011.02.012
  • NAID: 120003141452
  • Peer Reviewed
• [Presentation] Genetic CETP Deficiency Associated With Lower Coronary Stenosis Index in Dyslipdemic Patients in Japan (2014)
  • Author(s): Nohara A, Yoshida M, Okazaki S, Inoue T, Mori M, Nakanishi C, Kawashiri M-A, Yagi K, Inazu A, Yamagishi M, Mabuchi H.
  • Organizer: The 82nd Congress of the European Atherosclerosis Society
  • Place of Presentation: Madrid, Spain
• [Presentation] シンポジウム3:日本における原発性高脂血症の現状家族性高コレステロール血症の診断および治療の課題 (2013)
  • Author(s): 野原淳
  • Organizer: 第45回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Usefulness of FH Gene Test in Patients with Dyslipidemia (2013)
  • Author(s): Nohara A, Ohtani R, Noguchi T, Inoue T, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Inazu A, Yamagishi M, Mabuchi H
  • Organizer: 第45回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Common PCSK9 E32K Variant as Genetic Background of Familial Combined Hyperlipidemia (2013)
  • Author(s): Nohara A, Noguchi T, Inoue T, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Inazu A, Yamagishi M, Mabuchi H
  • Organizer: The 81st European Atherosclerosis Society Congress
  • Place of Presentation: Lyon, France
• [Presentation] Common PCSK9 E32K Variant as Genetic Background of Familial Combined Hyperlipidemia (2013)
  • Author(s): Nohara A, Noguchi T, Inoue T, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Inazu A, Yamagishi M, Mabuchi H
  • Organizer: 第77回日本循環器学会学術総会
  • Place of Presentation: 横浜
• [Presentation] シンポジウム３：日本における原発性高脂血症の現状 家族性高コレステロール血症の診断および治療の課題. (2013)
  • Author(s): 野原 淳
  • Organizer: 第45回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京・京王プラザ
  • Invited
• [Presentation] Usefulness of FH Gene Test in Patients with Dyslipidemia. (2013)
  • Author(s): Nohara A, Ohtani R, Noguchi T, Inoue T, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Inazu A, Yamagishi M, Mabuchi H.
  • Organizer: 第45回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京・京王プラザ
• [Presentation] Common PCSK9 E32K Variant as Genetic Background of Familial Combined Hyperlipidemia. (2013)
  • Author(s): Nohara A, Noguchi T, Inoue T, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Inazu A, Yamagishi M, Mabuchi H.
  • Organizer: The 81st European Atherosclerosis Society Congress
  • Place of Presentation: Lyon, France
• [Presentation] Impact of ER-Stress Affecting Variant of XBP-1 Gene on Lipids, Diabetes, Chronic Kidney Disease, and Coronary Artery Disease (2012)
  • Author(s): Nohara A, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Inazu A, Kobayashi J, Yamagishi M, Mabuchi H
  • Organizer: American Heart Association's Scientific Sessions, 2012
  • Place of Presentation: Los Angeles (USA)
• [Presentation] Triglyceride-Rich High-Density Lipoprotein Composition as Residual Risk Biomarker of Coronary Artery Disease Including Reduced eGFR and Pre-diabetes (2012)
  • Author(s): Nohara A, Inazu A, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Kobayashi J, Yamagishi M, Mabuchi H
  • Organizer: American Heart Association's Scientific Sessions
  • Place of Presentation: Los Angeles (USA)
• [Presentation] HDL-C Was Negatively Associated with Achilles' Tendon Thickening among Genetically Confirmed Familial Hypercholesterolemia (2012)
  • Author(s): Nohara A, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Inazu A, Kobayashi J, Yamagishi M, Mabuchi H
  • Organizer: HDL Satellite Symposium 2012
  • Place of Presentation: Cairns, AUS
• [Presentation] Hypertriglyceridemia eliminates positive correlations of plasma CETP with LDL-C and with Lp(a) (2012)
  • Author(s): Nohara A, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Inazu A, Kobayashi J, Yamagishi M, Mabuchi H
  • Organizer: XVI International Symposium on Atherosclerosis 2012
  • Place of Presentation: Sydney, AUS
• [Presentation] Triglyceride-Rich High-Density Lipoprotein Composition as Residual Risk Biomarker of Coronary Artery Disease Including Reduced eGFR and Pre-diabetes. (2012)
  • Author(s): Nohara A, Inazu A, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Kobayashi J, Yamagishi M, Mabuchi H.
  • Organizer: American Heart Association's Scientific Sessions, 2012
  • Place of Presentation: Los Angeles Convention Center, Los Angeles (USA)
• [Presentation] Impact of ER-Stress Affecting Variant of XBP-1 Gene on Lipids, Diabetes, Chronic Kidney Disease, and Coronary Artery Disease. (2012)
  • Author(s): Nohara A, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Inazu A, Kobayashi J, Yamagishi M, Mabuchi H.
  • Organizer: American Heart Association's Scientific Sessions, 2012
  • Place of Presentation: Los Angeles Convention Center, Los Angeles (USA)
• [Presentation] Impact of “Isolated” and “Non-isolated” Low Levels of HDL-C (2012)
  • Author(s): Nohara A, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri MA, Yagi K, Inazu A, Kobayashi J, Yamagishi M, Mabuchi H.
  • Organizer: 第44回日本動脈硬化学会総会・学術集会
  • Place of Presentation: ヒルトン福岡シーホーク，福岡県
• [Presentation] Hypertriglyceridemia eliminates positive correlations of plasma CETP with LDL-C and with Lp(a) (2012)
  • Author(s): Nohara A, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri M, Yagi K, Inazu A, Kobayashi J, Yamagishi M, Mabuchi H
  • Organizer: XVI International Symposium on Atherosclerosis
  • Place of Presentation: Sydney Convention and Exhibition Centre (Australia)
• [Presentation] Normalizing Pre-β1-HDL Levels with Eicosapentaenoic Acid Add-on to Atorvastatin (2012)
  • Author(s): Nohara A, Kobayashi J, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri M, Yagi K, Inazu A, Yamagishi M, Mabuchi H
  • Organizer: 第76回日本循環器学会総会・学術集会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] シンポジウム・心血管疾患予防のための新しいバイオマーカーImpact of Triglyceride-Rich High-Density Lipoprotein Composition as a New Marker for Development of Angiographic Coronary Artery Disease (2011)
  • Author(s): Nohara A, Inazu A, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri M, Yagi K, Kobayashi J, Yamagishi M, Mabuchi H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] シンポジウム・我が国に於ける家族性高コレステロール血症我が国に於けるFHの疫学とCHDへのリスク (2011)
  • Author(s): 野原淳,野口徹,小林淳二,多田隼人,森三佳,中西千明,川尻剛照,八木邦公,稲津明広,山岸正和,馬渕宏
  • Organizer: 第43回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 札幌
• [Presentation] "Intra-Individual Variability" of Fasting Lipids in Primary Hyperlipidemia is Associated With Fatty Liver, Hyperapobetalipoproteinemia and Advanced Coronary Artery Disease, But Not With Insulin Resistance (2011)
  • Author(s): Nohara A, Yagi K, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri M, Inazu A, Kobayashi J, Yamagishi M, Mabuchi H
  • Organizer: American Diabetes Association 71st Scientific Sessions
  • Place of Presentation: San Diego Convention Center (USA)
• [Presentation] シンポジウム・心血管疾患予防のための新しいバイオマーカー Impact of Triglyceride-Rich High-Density Lipoprotein Composition as a New Marker for Development of Angiographic Coronary Artery Disease (2011)
  • Author(s): Nohara A, Inazu A, Noguchi T, Tada H, Mori M, Nakanishi C, Kawashiri M, Yagi K, Kobayashi J, Yamagishi M, Mabuchi H
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: パシフィコ横浜(横浜)
• [Remarks]
  • URL: http://fh-gene-labo.w3.kanazawa-u.ac.jp