Quality, function and genetic assessments of NO, ACE and HDL in patients with coronary artery disease
Quality, function and genetic assessments of NO, ACE and HDL in patients with coronary artery disease
批准号:
09670773
负责人:
SAKU Keijiro
金额:
$2.3万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1997
资助国家:
日本
项目状态:
已结题
起止时间:
1997 至 1999
中文摘要
1.The fractional esterification rate of cholesterol(C)in apolipoprotein B-depleted plasma(FER I D2 HDL Ii)is a functional assay of high density lipoprotein(HDL)。In the case-control study[with/without angiographically defined coronary artery disease(CAD)],we found that high FER ei D2 HDL文件D2 was associated with an increased risk of CAD.The association between FER I D2 HDL文件D2 and CAD was not eliminated by adjusting for potential confounders and HDL-C levels,and the interaction between FER I D 2 HDL文件D2 and HDL-C was significant.FER D 2 HDL D 2 is an independent risk factor for CAD and the combination of FER D 2 HDL D 2 and HDL-C could be a potent indicator for CAD.2.The association among insulin resistance,as assessed by the homeostasis model assessment,HDL-C,and CAD was investigated in a case-control study。Cases were patients with angiographically defined CAD and controls were matched with cases with regard to gender and age.Cases were characterized by hyperinsulinemia and norm…More al glucose tolerance。Multivariate conditional logistic regression analysis indicated that insulin resistance and HDL-C were independently associated with CAD,but a much stronger association was found between hyperinsulinemic hypoalphalipoproteinemia and CAD.Low HDL-C and hyperinsulinemia synergistically increased the risk of CAD.3.Both nitric oxide(NO)and angiotensin converting enzyme(ACE)play important roles in maintaining endothelium-dependent relaxation/contraction,and in inhibiting/activating cell proliferation,adhesion and chemotaxis.We screened the missense Glu298 Asp variant of the eNOS gene and ACE I/D polymorphism in1002 patients with/without CAD。In diabetic patients,none of the combinations of eNOS and ACE gene polymorphism were related to CAD,while in non-DM patients(n=727),the combination of the missense Glu298 Asp variant(TT+TG)and the ACE-DD genotype was found to be a significant predictor of CAD,and other genotypic combinations were not。The combination of the missense Glu298Asp eNOS variant with the ACE-DD genotype may be a marker of CAD in non-DM patients.4。The association between ACE gene polymorphism and insulin resistance(IR)was investigated in patients with angina pectoris.Patients with the ACE-ID genotype had significantly lower IR,as assessed by an oral glucose tolerance test(OGTT)and by homeostatic model assessment(HOMA),compared to those with the ACE-II genotype。Patients were divided into two groups with low and high HOMA-IR,and the I allele was seen more frequently in the high HOMA-IR group than in the low HOMA-IR group.Logistic regression analysis showed that the odds ratio for insulin resistance in patients with the II genotype,compared to those with the ID and DD genotypes,was4.0,with and without adjusting for the presence of significant coronary atheroscierosis。The patients with the ID and DD genotypes were associated with a significantly lower risk of insulin resistance,compared to those with the II genotype。Less:Less
英文摘要
1. The fractional esterification rate of cholesterol (C) in apolipoprotein B-depleted plasma (FERィイD2HDLィエD2) is a functional assay of high density lipoprotein (HDL). In the case-control study [with/without angiographically defined coronary artery disease (CAD)], we found that high FERィイD2HDLィエD2 was associated with an increased risk of CAD. The association between FERィイD2HDLィエD2 and CAD was not eliminated by adjusting for potential confounders and HDL-C levels, and the interaction between FERィイD2HDLィエD2 and HDL-C was significant. FERィイD2HDLィエD2 is an independent risk factor for CAD and the combination of FERィイD2HDLィエD2 and HDL-C could be a potent indicator for CAD.2. The association among insulin resistance, as assessed by the homeostasis model assessment, HDL-C, and CAD was investigated in a case-control study. Cases were patients with angiographically defined CAD and controls were matched with cases with regard to gender and age. Cases were characterized by hyperinsulinemia and norm … More al glucose tolerance. Multivariate conditional logistic regression analysis indicated that insulin resistance and HDL-C were independently associated with CAD, but a much stronger association was found between hyperinsulinemic hypoalphalipoproteinemia and CAD. Low HDL-C and hyperinsulinemia synergistically increased the risk of CAD.3. Both nitric oxide (NO) and angiotensin converting enzyme (ACE) play important roles in maintaining endothelium-dependent relaxation/contraction, and in inhibiting/activating cell proliferation, adhesion and chemotaxis. We screened the missense Glu298Asp variant of the eNOS gene and ACE I/D polymorphism in 1002 patients with/without CAD. In diabetic patients, none of the combinations of eNOS and ACE gene polymorphism were related to CAD, while in non-DM patients (n=727), the combination of the missense Glu298Asp variant (TT+TG) and the ACE-DD genotype was found to be a significant predictor of CAD, and other genotypic combinations were not. The combination of the missense Glu298Asp eNOS variant with the ACE-DD genotype may be a marker of CAD in non-DM patients.4. The association between ACE gene polymorphism and insulin resistance (IR) was investigated in patients with angina pectoris. Patients with the ACE-ID genotype had significantly lower IR, as assessed by an oral glucose tolerance test (OGTT) and by homeostatic model assessment (HOMA), compared to those with the ACE-II genotype. Patients were divided into two groups with low and high HOMA-IR, and the I allele was seen more frequently in the high HOMA-IR group than in the low HOMA-IR group. Logistic regression analysis showed that the odds ratio for insulin resistance in patients with the II genotype, compared to those with the ID and DD genotypes, was 4.0, with and without adjusting for the presence of significant coronary atheroscierosis. The patients with the ID and DD genotypes were associated with a significantly lower risk of insulin resistance, compared to those with the II genotype. Less
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Saku K., Zhang B., et al.: "Associations among serum lipoprotein(a) [Lp(a)] levels, apolipoprotein(a) phenotypes, and myocardial infarction in patients with extremely low and high serum levels of Lp(a)"Jpn Circ J. 63. 659-665 (1999)
Saku K.、Zhang B. 等人:“血清 Lp(a) 水平极低和极高的患者的血清脂蛋白 (a) [Lp(a)] 水平、载脂蛋白 (a) 表型与心肌梗死之间的关联
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Saku K.,Zhang B.,et al.: "Associations among serum lipoprotein(a)[Lp(a)]levels,apolipoprotein(a)phenotypes,and myocardial infarction in patients with extremely low and high serum levels of Lp(a)."Jpn Circ J. 63. 659-665 (1999)
Saku K.,Zhang B.,et al.:“血清脂蛋白(a)[Lp(a)]水平、载脂蛋白(a)表型与血清 Lp(a)水平极低和极高的患者中的心肌梗死之间的关联
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Bai H.,Saku K.,et.al.: "Polymorphism of the apolipoprotein A-IV gene and its significance in lipid metabolism and coroanry heart disease in a Japanese population." Europ J Clin Invest.26. 1115-1124 (1996)
Bai H.,Saku K.,et.al.:“载脂蛋白 A-IV 基因的多态性及其在日本人群脂质代谢和冠心病中的意义。”
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Saku K.,von Eckardstein A.,Zhang B.,Liu R.,Jimi S.,Ou JF.,Ohta T.Assmann G.,Arakawa K.: "In vivo kinetics of human apolipoprotein A-I variants in rabbits."Europ J Clin Invest. 29. 196-203 (1998)
Saku K.、von Eckardstein A.、Zhang B.、Liu R.、Jimi S.、Ou JF.、Ohta T.Assmann G.、Arakawa K.:“人载脂蛋白 A-I 变体在兔体内的体内动力学。”Europ
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Kiyonaga A., Imai K., Zhang B., Saku K.: "Exercise Prevent Comm Dis"Springer-Verlag. 10 (1999)
Kiyonaga A.、Imai K.、Zhang B.、Saku K.:“Exercise Prevent Comm Dis”Springer-Verlag。
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共 61 条
New diagnostic and therapeutic strategies for atherosclerosis using newly developed apolipoprotein A-I mimetic peptide
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批准号:24591123
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$3.24万
-
财政年份:2012
-
负责人:SAKU Keijiro
-
依托单位:
Possibility of drug discovery : Development of new peptide type of reconstituted HDL
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批准号:21590960
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.75万
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财政年份:2009
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负责人:SAKU Keijiro
-
依托单位:
Advanced medical technology on cardiovascular disease- Elucidation of the molecular mechanism and the application on various pathological conditions for the establishment of HDL therapy
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批准号:18590826
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.56万
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财政年份:2006
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负责人:SAKU Keijiro
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依托单位:
Therapeutic strategy for atherosclerosis targeting for CETP
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批准号:12670712
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.05万
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财政年份:2000
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负责人:SAKU Keijiro
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依托单位:
Quantity, function and genetics of HDL as an indicator of CHD.
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批准号:07670827
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$1.34万
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财政年份:1995
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负责人:SAKU Keijiro
-
依托单位:
HDL-apoAI gene expression and its kinetics in vivo
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批准号:04671503
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项目类别:Grant-in-Aid for General Scientific Research (C)
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资助金额:$0.9万
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财政年份:1992
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负责人:SAKU Keijiro
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依托单位:
HDL-apoAI and its isoproteins kinetics in rabbits and gene expressin of apoAI.
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批准号:02671114
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项目类别:Grant-in-Aid for General Scientific Research (C)
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资助金额:$1.02万
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财政年份:1990
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负责人:SAKU Keijiro
-
依托单位:
海外基金