Abstract:
BACKGROUND AND AIMS:Clinical interventions targeting nonlipid risk factors are needed given the high residual risk of atherothrombotic events despite effective control of dyslipidemia. Dickkopf-1 (DKK1) plays a lipid-independent role in vascular pathophysiology but its involvement in atherosclerosis development and its therapeutic attractiveness remain to be established. METHODS:Patient data, in vitro studies and pharmacological intervention in murine models of atherosclerosis were utilized. RESULTS:In patients' material (n = 127 late stage plaque specimens and n = 10 control vessels), DKK1 mRNA was found to be higher in atherosclerotic plaques versus control arteries. DKK1 protein was detected in the luminal intimal area and in the necrotic core of plaques. DKK1 was released from isolated primary human platelets (~12 - 21-fold) and endothelial cells (~1.4-2.5-fold) upon stimulation with different pathophysiological stimuli. In ApoE-/- and Ldlr-/- mice, plasma DKK1 concentrations were similar to those observed in humans, whereas DKK1 expression in different atheroprone arterial segments was very low/absent. Chronic treatment with a neutralizing DKK1 antibody effectively reduced plasma concentrations, however, plaque lesion area was not reduced in ApoE-/- and Ldlr-/- mice fed a western diet for 14 and 16 weeks. Anti-DKK1 treatment increased bone volume and bone mineral content. CONCLUSIONS:Functional inhibition of DKK1 with an antibody does not alter atherosclerosis progression in classical murine models. This may reflect the absence of DKK1 expression in plaques and more advanced animal disease models could be needed to evaluate the role and therapeutic attractiveness of DKK1 in late stage complications such as plaque destabilization, calcification, rupture and thrombosis.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
Rakipovski G,Rolin B,Barascuk N,Lund HE,Bjørn Bonde MF,Djordjevic D,Wulff-Larsen PG,Petersen M,Kirk RK,Hultman K,Manfe V,Blume N,Zahn S,Lengquist M,Maegdefessel L,Hovingh GK,Conde-Knape K,Hedin U,Matic L,Nyberg Mdoi
10.1016/j.atherosclerosis.2020.10.001subject
Has Abstractpub_date
2020-12-01 00:00:00pages
1-9eissn
0021-9150issn
1879-1484pii
S0021-9150(20)30562-1journal_volume
314pub_type
杂志文章相关文献
ATHEROSCLEROSIS文献大全abstract:OBJECTIVE:The aim of this study was to determine the relationship between brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) in a large multi-ethnic elderly cohort. BACKGROUND:Brachial flow-mediated dilation (FMD) is a physiologic measure and carotid IMT is an anatomic structural measure of...
journal_title:Atherosclerosis
pub_type: 杂志文章,多中心研究
doi:10.1016/j.atherosclerosis.2007.07.032
更新日期:2008-04-01 00:00:00
abstract:BACKGROUND AND AIMS:The impact of treatment strategies on outcomes in patients with stable coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) according to presenting angina has not been rigorously assessed. METHODS:We performed a patient-level pooled-analysis (n = 5027) of patients with stable CAD and T...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2018.04.005
更新日期:2018-10-01 00:00:00
abstract::To determine whether high prevalence of small dense low-density lipoprotein (LDL) in non-insulin-dependent diabetes (NIDDM) with nephropathy is directly associated with kidney damage, we measured LDL particle size by non-denaturing 2-16% gradient polyacrylamide gel electrophoresis in non-diabetic patients with primary...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/s0021-9150(98)00150-6
更新日期:1998-11-01 00:00:00
abstract::Over 200 risk factors for cardiovascular disease (CVD) have now been identified. Among these, the three most important are (1) abnormal lipids, including the fact that there are more than 15 types of cholesterol-containing lipoproteins and four different types of triglyceride-rich particles, some of which are very ath...
journal_title:Atherosclerosis
pub_type: 杂志文章,评审
doi:10.1016/0021-9150(96)05851-0
更新日期:1996-07-01 00:00:00
abstract::Five homozygous patients with familial hypercholesterolemia (FH) are described. Their serum cholesterol levels were between 603 and 907 mg/dl, with an average of 714 mg/dl. The mean value of serum cholesterol levels of the obligate heterozygous parents was 270 mg/dl. In the patient group, 87% of the serum cholesterol ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(85)90042-5
更新日期:1985-11-01 00:00:00
abstract::Short-term exercise training has been associated with improved endothelial-dependent vasodilation, but the impact of long-term habitual physical activity on vascular reactivity is not established. We studied the correlation between self-reported, habitual physical activity and vasoreactivity in non-smoking, non-diabet...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/s0021-9150(01)00529-9
更新日期:2001-12-01 00:00:00
abstract::Human serum paraoxonase 1 (PON1) is associated with high-density lipoprotein, and inhibits oxidative modification of low-density lipoprotein in vitro. Therefore, PON1 is supposed to protect against atherosclerosis in vivo. In this study, we investigated the direct effect of Sp1 on PON1 transcription in HepG2 cells usi...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2004.05.029
更新日期:2004-10-01 00:00:00
abstract::In type 2 diabetics, the progression of atherosclerosis is more rapid than the general population and 80% of these patients will die of an atherosclerotic event. Since in these patients hyperglycemia per se confers increased risk for cardiovascular disease (CVD), the presence of even borderline-high-risk LDL-C signals...
journal_title:Atherosclerosis
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.atherosclerosis.2005.02.020
更新日期:2005-10-01 00:00:00
abstract::To test the hypothesis of altered energy production in aortic sites predisposed to lesion formation, both coupled oxidative phosphorylation (evaluated from P/O ratios) and control of the energy-linked (ATP) NADH transhydrogenase were examined in muscular cushions at the celiac artery bifurcation. Comparisons were made...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(80)90230-0
更新日期:1980-06-01 00:00:00
abstract::Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which substitution of the amino acid glutamine for arginine at position 3500 in the apoprotein B molecule results in LDL particles which bind poorly to the LDL receptor. To date, patients with FDB ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(93)90130-m
更新日期:1993-01-25 00:00:00
abstract::Estrogen use is associated with protection from cardiovascular disease in postmenopausal women. This benefit appears to be magnified among women with pre-existing heart disease. The possible bias of intrinsically better health in women using estrogen has not been ruled out in observational studies. Therefore, two doub...
journal_title:Atherosclerosis
pub_type: 杂志文章,评审
doi:10.1016/0021-9150(94)05379-w
更新日期:1994-10-01 00:00:00
abstract::In the process of screening apolipoprotein (apo) E genotypes in a population of subjects with lipid abnormalities, we have identified five subjects (one homozygote and four heterozygotes) with an abnormal 109 base pairs band following apo E restriction isotyping of amplified DNA with the restriction endonuclease CfoI....
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(95)06745-0
更新日期:1996-04-26 00:00:00
abstract:BACKGROUND AND AIMS:Results from prospective studies evaluating the relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and incident peripheral arterial disease (PAD) have been mixed. We investigated whether higher Lp-PLA2 levels are associated with increased risk of incident PAD an...
journal_title:Atherosclerosis
pub_type: 杂志文章,多中心研究
doi:10.1016/j.atherosclerosis.2017.11.007
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND AND AIMS:Little is known about the role of liver enzymes as predictors of non-liver-related morbidity and mortality. The ideal cardiovascular health (CVH) score proposed by the American Heart Association (AHA) can be used to predict mortality and morbidity. We investigated the association of the CVH score wi...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2018.11.012
更新日期:2019-05-01 00:00:00
abstract::To examine the relationship between metabolic syndrome and endothelial dysfunction, we investigated cross-sectionally the correlation between metabolic risk factors and urinary excretion of cyclic guanosine 3',5'-monophosphate (cGMP), a second messenger of nitric oxide (NO), in 1541 Japanese men and women aged 40-79 y...
journal_title:Atherosclerosis
pub_type: 杂志文章,多中心研究
doi:10.1016/j.atherosclerosis.2006.02.032
更新日期:2007-02-01 00:00:00
abstract::Recent studies demonstrate important roles for inflammation in development of atherosclerosis with current attention focusing on interactions of inflammation with traditional lipoprotein risk factors. Since the nature of such relationships is largely unknown, we sought to investigate interactions of inflammation with ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2005.09.012
更新日期:2006-07-01 00:00:00
abstract::Polar coordinate mapping was used to determine the rate of growth of individual sudanophilic lesions on the aortic wall around several major branches of the aortae of cholesterol fed rabbits. Four groups, with 6 8-month old male albino white rabbits in each, were used in the study. One group served as a control and th...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(76)90043-5
更新日期:1976-10-01 00:00:00
abstract:BACKGROUND:Oxidation processes play an important role in atherogenesis. Bilirubin IXalpha is recognised as a potent antioxidant. In the present study, we assessed the role of elevated serum bilirubin levels in the prevention of ischemic heart disease (IHD). METHODS:The occurrence of IHD was determined in Gilbert syndr...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/s0021-9150(01)00601-3
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND:Heterozygous familial hypercholesterolemia (heFH) is a common autosomal dominant hereditary disorder caused by mutations in the LDL-receptor gene that lead to elevated plasma levels of low-density lipoprotein-cholesterol (LDL-c). Robust lowering of LDL-c levels is essential for risk reduction of premature ca...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2009.09.014
更新日期:2010-03-01 00:00:00
abstract::The cell-adhesion molecule CD44 likely participates in atherosclerosis development. We have shown previously that pro-inflammatory cytokines affect CD44 expression. Therefore, this work examined the role of elevated CD44 levels in human macrophages. Macrophages from human atherosclerotic subjects (n=15) showed elevate...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2006.03.020
更新日期:2007-02-01 00:00:00
abstract::Endothelial cells (EC) were harvested by 0.1% collagenase treatment for adult human thoracic aortas obtained 1-3 h after sudden death. At least 35-70% of EC were removed from the intimal surface of aorta, 90-95% of them being viable. Plating efficiency was 70-80%. Monolayer formation was achieved at a seeding density ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(86)90027-4
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:A hallmark feature of atherosclerosis is inflammation mediated by prostaglandins (PGs) catalyzed by the enzyme cyclooxygenase (COX). The present study explored whether the COX-2 G-765C polymorphism contributes to increased incidence of coronary heart disease (CHD) or stroke in the large prospective Atheroscl...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2007.02.010
更新日期:2008-02-01 00:00:00
abstract::Heritability of plasma apolipoprotein (apo) A-I, apo B, and low density lipoprotein (LDL) subclasses and concordance for lipoprotein(a) excess were assessed in 109 monozygotic (MZ) and 113 dizygotic (DZ) twin pairs participating in the third examination of the National Heart, Lung, and Blood Institute Twin Study. The ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(91)90191-5
更新日期:1991-11-01 00:00:00
abstract:BACKGROUND AND AIMS:Proteoglycan 4 (Prg4) has a high structural similarity with the established atherosclerosis-modulating proteoglycan versican, but its role in atherogenesis is still unknown. Therefore, the impact of Prg4 deficiency on macrophage function in vitro and atherosclerosis susceptibility in vivo was invest...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2018.05.008
更新日期:2018-07-01 00:00:00
abstract:OBJECTIVE:Lipoprotein(a) [Lp(a)] consists of apolipoprotein B-100 (apoB-100) as part of an LDL-like particle and the covalently linked glycoprotein apolipoprotein(a) [apo(a)]. Detailed mechanisms of its biosynthesis, assembly, secretion and catabolism are still poorly understood. To address the Lp(a) assembly mechanism...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2012.09.031
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND AND AIMS:Galectin-3 binding protein (Gal-3BP) has been associated with inflammation and cancer, however, its role in coronary artery disease (CAD) and cardiovascular outcome remains unclear. METHODS:Gal-3BP plasma levels were measured by ELISA in 2922 individuals from the LURIC study (62.7 ± 10.6 years, 62....
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2017.03.031
更新日期:2017-05-01 00:00:00
abstract::The insulin response to a standard oral glucose tolerance test (OGTT) and other anthropometric and biochemical risk factors for coronary heart disease (CHD) were measured in a random sample of 107 Edinburgh men, who were initially studied in 1976 when they were 40 and who were reexamined in 1988-89. Fasting glucose an...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(92)90188-m
更新日期:1992-05-01 00:00:00
abstract:BACKGROUND AND AIMS:Dietary long-chain (≥20 carbons) n-3 polyunsaturated fatty acids (PUFAs) reduce atherosclerosis and enhance macrophage autophagy activation. How macrophage autophagy impacts atherosclerotic progression, particularly when comparing dietary n-3 PUFA supplementation vs. saturated fat feeding, is unknow...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/j.atherosclerosis.2020.01.004
更新日期:2020-02-01 00:00:00
abstract::The effect of administering blackgram (Phaseolus mungo) fiber (isolated as neutral detergent residue) at the 30% dietary level has been studied with regard to lipid concentration in the tissues and that of biliary and fecal bile acids and sterols. Rats were fed a high fat-cholesterol diet and compared with those fed a...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(79)90196-5
更新日期:1979-05-01 00:00:00
abstract::Tendon xanthoma are a hallmark of familial hypercholesterolemia and are among its earliest clinical manifestations. Achilles tendon size, advanced to a generally accepted marker, is virtually specific for the disease and easily accessible for measurement. Hypercholesterolemic patients with coronary heart disease have ...
journal_title:Atherosclerosis
pub_type: 杂志文章
doi:10.1016/0021-9150(88)90242-0
更新日期:1988-12-01 00:00:00