Abstract:
BACKGROUND AND AIM:Hypercholesterolaemia is a major risk factor for atherosclerosis. Cholesterol is modulated by genetic and environmental factors. An important regulatory pathway is controlled by the sterol-regulatory element-binding proteins (SREBPs) and the SREBP cleavage-activating protein (SCAP). Both SREBP-2 and SCAP are candidates to contribute to the development of atherosclerosis. We investigated the possible effects of the variability of proteins involved in this regulatory pathway on plasma lipids among familial hypercholesterolaemia patients. METHODS AND RESULTS:Single nucleotide polymorphisms (SNPs) in the genes encoding SREBP-2 and SCAP causing amino acid changes at positions 595 (595G/A) and 796 (796I/V), respectively, were genotyped in 801 FH individuals originating from Israel, The Netherlands, and Switzerland. A linear regression model to examine the associations between SREBP-2 and SCAP isoforms and lipid and lipoprotein levels was used. In females, homozygosity either for the SREBP-2-595A or for the SCAP-796I isoform was associated with higher LDL-cholesterol plasma concentrations (14.7 mg/dl and 20.3 mg/dl, respectively). Surprisingly, heterozygosity for the combination SREBP-2-595A/SCAP-796I was associated with a decrease of 30.28 mg/dl in LDL-C (p-value for gene-gene interaction=0.09). No such effect was observed among FH males. Subgroup analysis considering the most frequent (N>/=24) LDL receptor mutations (del191-2, ins313+1-2, C660X, E207K, S285L) revealed further gene-dosage- and gender-dependent effects of the SCAP mutations on LDL-cholesterol concentrations (p=0.0345). These effects were, however, not present when less frequent LDL receptor mutations were investigated. CONCLUSIONS:These results suggest a possible gene-gene interaction between the genes encoding SREBP-2 and SCAP that modulate plasma lipids in a strictly gender-specific fashion. Further investigation is needed to confirm this effect. A study in a larger FH group or in non-FH hypercholesterolaemic subjects may further define the role of this regulatory mechanism in determining plasma lipid concentration.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
Durst R,Jansen A,Erez G,Bravdo R,Butbul E,Ben Avi L,Shpitzen S,Lotan C,Leitersdorf E,Defesche J,Friedlander Y,Meiner V,Miserez ARdoi
10.1016/j.atherosclerosis.2006.01.001keywords:
subject
Has Abstractpub_date
2006-12-01 00:00:00pages
443-50issue
2eissn
0021-9150issn
1879-1484pii
S0021-9150(06)00025-6journal_volume
189pub_type
杂志文章,多中心研究相关文献
ATHEROSCLEROSIS文献大全abstract:BACKGROUND:Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine implicated in atherosclerotic plaque formation. We investigated whether circulating TNFalpha is prospectively associated with myocardial infarction (MI) or stroke in the older general population, independently of established cardiovascula...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2008.12.001
更新日期:2009-07-01 00:00:00
abstract:OBJECTIVE:Recent data suggests that cholesteryl ester transfer protein (CETP) activity may interact with acute stress conditions via inflammatory-oxidative response and thrombogenesis. We investigated this assumption in patients with ST-elevation myocardial infarction (STEMI). METHODS:Consecutive patients with STEMI (...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2014.10.104
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND:In Europeans, 45 genetic risk variants for coronary artery disease (CAD) have been identified in genome-wide association studies. We constructed a genetic risk score (GRS) of these variants to estimate the effect on incidence and clinical predictability of myocardial infarction (MI) and CAD. METHODS:Genotyp...
journal_title:Atherosclerosis
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.atherosclerosis.2015.03.022
更新日期:2015-06-01 00:00:00
abstract:OBJECTIVE:Recent studies have suggested that circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL) is a useful marker for the identification of patients with coronary artery disease (CAD). However, the role of MDA-LDL in atherogenic mechanisms has not yet been fully determined. METHOD AND RESULTS:We i...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2004.09.013
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVE:Limited evidence suggests NT-proBNP improves prediction of coronary heart disease (CHD) events but further data are needed, especially in people without pre-existing CHD and in women. METHODS:We measured NT-proBNP in serum from 162 women with incident CHD events and 1226 controls (60-79 years) in a case-cont...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2009.09.016
更新日期:2010-03-01 00:00:00
abstract:OBJECTIVES:To analyze the relationship between office and ambulatory heart rate, and its variability, and arterial stiffness in patients with primary arterial hypertension. METHODS:A cross-sectional study was conducted in a primary care setting, with the inclusion of 356 hypertensive patients aged 30-80 years. Office ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2011.03.037
更新日期:2011-08-01 00:00:00
abstract:OBJECTIVE:To investigate the hypothesis that COMP can influence the morphology, stability and size of murine atherosclerotic lesions. METHODS:ApoE- and ApoE/COMP-knockout mice were fed a high-fat diet to develop atherosclerotic plaques at lesion sites of three different types; inflammatory and fibrous plaques induced ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2014.07.029
更新日期:2014-10-01 00:00:00
abstract::Oxidation of low density lipoprotein (LDL) is implicated in the pathogenesis of atherosclerosis. In this study the susceptibility to oxidation of LDL (from patients with atherosclerosis) is related to the progression of the disease. LDL were isolated from 37 patients with demonstrable atherosclerotic plaques. The susc...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(94)05401-4
更新日期:1995-01-06 00:00:00
abstract::Plasma cholesterol was lower in spontaneously hypertensive rats (SHR), while plasma triglyceride and free fatty acid were increased in comparison with control normotensive Wistar-Kyoto (WK) rats. Correspondingly, [1-14C]-acetate incorporation into liver cholesterol was clearly decreased in SHR as compared with WK. As ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(77)90171-x
更新日期:1977-11-01 00:00:00
abstract::There is clear evidence of lipoprotein oxidation in atherosclerotic lesions. Animal studies and observational prospective human cohort studies have been interpreted as supporting a role for antioxidants in the prevention of coronary heart disease (CHD). However, firm recommendations to take antioxidant supplements to ...
journal_title:Atherosclerosis
pub_type: 杂志文章,评审
doi:10.1016/s0021-9150(02)00011-4
更新日期:2002-10-01 00:00:00
abstract::Tumor necrosis factor-alpha (TNF-alpha) is known to be a secretory product of activated macrophages. TNF-alpha activates endothelial cells, stimulates angiogenesis and induces proliferation of smooth muscle cells (SMCs). Therefore, TNF-alpha has been suggested to be actively involved in the inflammatory events associa...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(96)05863-7
更新日期:1996-08-23 00:00:00
abstract::In animal model studies, the uptake of chylomicron remnants after entering in the space of Disse occurs mainly by low-density lipoprotein (LDL) receptor and LDL receptor-related protein (LRP). In subjects, the relative importance of each one of these receptors for the clearance of chylomicron remnants is not fully und...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/s0021-9150(01)00661-x
更新日期:2002-04-01 00:00:00
abstract::The possibility that Fas/APO 1 is involved in the apoptosis of advanced human coronary atherosclerosis was examined in the present study. Coronary arteries with atherosclerosis were obtained from human hearts with chronic ischemic heart disease at cardiac transplantation. Normal vessels were used as controls. Fas/APO ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/s0021-9150(97)06099-1
更新日期:1997-06-01 00:00:00
abstract::The aims of this study were to determine whether non-invasive measurement of endothelial function in conduit arteries reflects that of subcutaneous resistance arteries measured in vitro and to examine whether there is an endothelial dysfunction also in resistance arteries in patients with a previous myocardial infarct...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2005.03.025
更新日期:2006-01-01 00:00:00
abstract::Smooth muscle cell (SMC) proliferation is a prominent feature of intimal hyperplasia after percutaneous coronary interventions. p27 is a critical regulator of cell proliferation. Our aims were to analyze the time course of p27 expression, Ki67 proliferative index, and apoptosis after angioplasty in the porcine coronar...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/s0021-9150(00)00421-4
更新日期:2000-12-01 00:00:00
abstract::Extensive research has been carried out in recent years to discover the potential risk factors contributing to cardiac allograft atherogenesis. Injury to endothelial cells has been regarded as an important early mechanism in the development of transplant atherosclerosis; it leads to the manifestation of epicardial and...
journal_title:Atherosclerosis
pub_type: 杂志文章,评审
doi:10.1016/s0021-9150(98)00106-3
更新日期:1998-09-01 00:00:00
abstract::The elevated carbon monoxide level found in tobacco smokers has been suggested as one etiologic factor linking it with atherosclerosis. Unquestionably carbon monoxide does induce some arterial wall hypoxia, which has been established as an atherogenic factor, but without knowing the extent and location of this hypoxia...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(78)90148-x
更新日期:1978-05-01 00:00:00
abstract::In the abdominal aortas of young mash-fed swine, intimal cell masses (pads, cushions) are located predominantly away from blood vessel orifices. They are found scattered throughout the aorta but nevertheless have a definite pattern of distribution. In the distal one half of the abdominal aorta, they are more frequent ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/s0021-9150(79)80007-6
更新日期:1979-11-01 00:00:00
abstract:BACKGROUND:Previous studies have found polymorphisms of the HDL receptor, SR-BI, to be associated with plasma HDL-C in women, but not men, suggesting a modifying role of estrogen. We examined whether the association between SR-BI genotypes and HDL-C is modified by use of unopposed estrogen in community-dwelling postmen...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2004.12.013
更新日期:2005-06-01 00:00:00
abstract:OBJECTIVE:We examined the risk of cardiovascular disease, stroke, ischaemic heart disease, and diabetes with the metabolic syndrome according to the new harmonised definition and its components using a national longitudinal data set from an Asian population. METHODS:Data of 9791 men and women aged 20+ from 1998 and 20...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2010.09.009
更新日期:2010-12-01 00:00:00
abstract::We studied the effect of probucol on lipoprotein composition and VLDL apo B turnover. In 7 hypercholesterolemic subjects, probucol therapy lowered mean total cholesterol, HDL cholesterol and HDL triglycerides, raised LDL triglycerides and did not change LDL cholesterol. LDL cholesterol:LDL triglycerides mass ratios fe...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(83)90058-8
更新日期:1983-06-01 00:00:00
abstract::Numerous studies have found polymorphisms in the lipoprotein lipase (LPL) gene to be associated with the risk of coronary artery disease (CAD), implicating LPL in the development of atherothrombotic disease. It remains controversial, however, whether LPL acts in a pro- or anti-atherogenic fashion. We quantitated activ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/s0021-9150(01)00752-3
更新日期:2002-07-01 00:00:00
abstract::We describe a rapid screening procedure to identify known DNA sequence changes in individuals diagnosed as having heterozygous familial hypercholesterolaemia (FH). The screening is made possible by combining a rapid DNA extraction protocol and small scale polymerase chain reaction DNA amplification, followed by oligon...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(91)90053-6
更新日期:1991-08-01 00:00:00
abstract:OBJECTIVE:Atherogenic dyslipidemia (AD), characterized by high plasma triglycerides and low HDL particles, is considered one of the main effectors of vascular damage associated with obesity, metabolic syndrome (MS) and type 2 diabetes. Adipocyte fatty acid-binding protein (FABP4) plasma concentrations have been linked ...
journal_title:Atherosclerosis
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.atherosclerosis.2012.02.003
更新日期:2012-05-01 00:00:00
abstract::We investigated the modulating effect of serum total triglycerides on the lipid composition of various lipoproteins, and on the response to gemfibrozil treatment. This placebo controlled study was conducted blind in 60 participants of the Helsinki Heart Study. An inverse relationship was observed between cholesterol c...
journal_title:Atherosclerosis
pub_type: 临床试验,杂志文章
doi:10.1016/0021-9150(90)90054-m
更新日期:1990-02-01 00:00:00
abstract::In the present study apoA-I (Lys 107del), a naturally occurring human apoA-I variant with a deletion of Lys 107, was expressed in E. coli to examine the effect of this mutation on lipid binding, cholesterol efflux and lecithin:cholesterol acyltranferase (LCAT) activation. Dimyristoyl phosphatidylcholine (DMPC) binding...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/s0021-9150(01)00496-8
更新日期:2001-11-01 00:00:00
abstract::Lipoprotein measurements in a group of 29 patients with massive proteinuria and without hypoalbuminemia, were compared with those observed in matched controls and patients with overt nephrotic syndrome to assess the influence of plasma albumin concentration and proteinuria in modulating blood lipid levels. Plasma apop...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(96)05905-9
更新日期:1996-10-25 00:00:00
abstract:BACKGROUND AND AIMS:A potential increased risk of cardiovascular events has been suggested for proton pump inhibitors (PPIs), the most commonly prescribed drugs for the management of upper gastrointestinal disorders. We aimed to estimate the risk of hospitalization for cardio/cerebrovascular (CV) events in a cohort of ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2018.08.035
更新日期:2018-10-01 00:00:00
abstract:OBJECTIVE:Recent studies have demonstrated that palmitic acid (PA) could regulate endothelial progenitor cells (EPCs) function (migration, proliferation, survival and angiogenesis) via various signal pathways, but the effect of PA on EPCs apoptosis and associated mechanisms are still elusive. METHODS:The human EPCs we...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2009.10.032
更新日期:2010-05-01 00:00:00
abstract::The single nucleotide polymorphisms (SNPs) apolipoprotein E (APOE) epsilon3/epsilon2/epsilon4, cholesteryl ester transfer protein (CETP) TaqIB, and apolipoprotein C3 (APOC3) -482 C>T have been associated with an atherogenic lipid profile and, in some studies, with increased cardiovascular risk. However, no data exist ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2007.10.030
更新日期:2008-07-01 00:00:00