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21.
Heterozygous familial hypercholesterolaemia is among the most common inherited dominant disorders, and is characterized by severely elevated LDL-cholesterol levels and premature cardiovascular disease. Although the cause of familial hypercholesterolaemia is monogenic, there is a substantial variation in the onset and severity of atherosclerotic disease symptoms. Additional atherogenic risk factors of environmental, metabolic and genetic origin, in conjunction with the LDL receptor defect, are presumed to influence the clinical phenotype in familial hypercholesterolaemia. The present review discusses recent developments in this field. 相似文献
22.
Hayden MR Clee SM Brooks-Wilson A Genest J Attie A Kastelein JJ 《Current opinion in lipidology》2000,11(2):117-122
Cellular cholesterol efflux, by which cholesterol is transported from peripheral cells to HDL acceptor molecules for transport to the liver, is the first step of reverse cholesterol transport. Two genetic disorders, Tangier disease and some cases of familial HDL deficiency, have defects of cellular cholesterol efflux. The recent discovery of mutations in the ABC1 gene, which encodes the cholesterol efflux regulatory protein, in both these disorders establishes cholesterol efflux regulatory protein as a rate-limiting factor in reverse cholesterol transport. 相似文献
23.
Clee SM Bissada N Miao F Miao L Marais AD Henderson HE Steures P McManus J McManus B LeBoeuf RC Kastelein JJ Hayden MR 《Journal of lipid research》2000,41(4):521-531
Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism, and has been hypothesized to exert either pro- or anti-atherogenic effects, depending on its localization. Decreased plasma LPL activity is associated with the high triglyceride (TG);-low HDL phenotype that is often observed in patients with premature vascular disease. In contrast, in the vessel wall, decreased LPL may be associated with less lipoprotein retention due to many potential mechanisms and, therefore, decreased foam cell formation. To directly assess this hypothesis, we have distinguished between the effects of variations in plasma and/or vessel wall LPL on atherosclerosis susceptibility in apoE-deficient mice. Reduced LPL in both plasma and vessel wall (LPL(+/-)E(-/-)) was associated with increased TG and increased total cholesterol (TC) compared with LPL(+/+)E(-/-) sibs. However despite their dyslipidemia, LPL(+/-)E(-/-) mice had significantly reduced lesion areas compared to the LPL(+/+)E(-/-) mice. Thus, decreased vessel wall LPL was associated with decreased lesion formation even in the presence of reduced plasma LPL activity. In contrast, transgenic mice with increased plasma LPL but with no increase in LPL expression in macrophages, and thus the vessel wall, had decreased TG and TC and significantly decreased lesion areas compared with LPL(+/+)E(-/-) mice. This demonstrates that increased plasma LPL activity alone, in the absence of an increase in vessel wall LPL, is associated with reduced susceptibility to atherosclerosis.Taken together, these results provide in vivo evidence that the contribution of LPL to atherogenesis is significantly influenced by the balance between vessel wall protein (pro-atherogenic) and plasma activity (anti-atherogenic). 相似文献
24.
25.
Phylogenetic utility of the nuclear gene arginine decarboxylase: an example from Brassicaceae 总被引:10,自引:2,他引:8
Arginine decarboxylase (ADC) is an important enzyme in the production of
putrescine and polyamines in plants. It is encoded by a single or low-copy
nuclear gene that lacks introns in sequences studied to date. The rate of
Adc amino acid sequence evolution is similar to that of ndhF for the
angiosperm family studied. Highly conserved regions provide several target
sites for PCR priming and sequencing and aid in nucleotide and amino acid
sequence alignment across a range of taxonomic levels, while a variable
region provides an increased number of potentially informative characters
relative to ndhF for the taxa surveyed. The utility of the Adc gene in
plant molecular systematic studies is demonstrated by analysis of its
partial nucleotide sequences obtained from 13 representatives of
Brassicaceae and 3 outgroup taxa, 2 from the mustard oil clade (order
Capparales) and 1 from the related order Malvales. Two copies of the Adc
gene, Adc1 and Adc2, are found in all members of the Brassicaceae studied
to data except the basal genus Aethionema. The resulting Adc gene tree
provides robust phylogenetic data regarding relationships within the
complex mustard family, as well as independent support for proposed tribal
realignments based on other molecular data sets such as those from
chloroplast DNA.
相似文献
26.
27.
Bisoendial RJ Kastelein JJ Peters SL Levels JH Birjmohun R Rotmans JI Hartman D Meijers JC Levi M Stroes ES 《Journal of lipid research》2007,48(4):952-960
C-reactive protein (CRP) has been suggested to exert direct adverse effects on the vasculature in experimental setups, including endothelial dysfunction and proinflammatory changes. Here, we assessed the consequences of 1.25 mg/kg highly purified recombinant human CRP, administered as an intravenous bolus, in six patients with familial hypercholesterolemia (FH) and six normocholesterolemic subjects. Endothelium-dependent and -independent vasoreactivity to serotonin and nitroprusside, respectively, were assessed using venous occlusion plethysmography before and after CRP infusion. For biochemical analyses, blood was drawn at different time points. At baseline, FH patients showed blunted endothelium-dependent vasodilation (maximum, 89.2 +/- 30.0% vs. 117.7 +/- 13.1% in normolipidemic subjects; P = 0.037). Procoagulant activity was also higher in FH patients, illustrated by increased prothrombin fragment 1+2 (F(1+2)) levels (P = 0.030) and plasminogen activator inhibitor type-1 (PAI-1) activity (P = 0.016). Upon CRP challenge, endothelium-dependent vasodilator capacity further deteriorated in FH patients (P = 0.029), whereas no change in vascular reactivity was observed in normolipidemic subjects. Additionally, coagulation activation was augmented in FH patients compared with normolipidemic subjects (P = 0.009 for F(1+2) levels; P = 0.018 and P = 0.003 for PAI-1 antigen and activity, respectively). No difference in inflammatory responses was observed between groups. In hypercholesterolemic patients, CRP aggravates endothelial dysfunction and also evokes augmented procoagulant responses. These findings suggest that particularly in hypercholesterolemia, CRP-lowering strategies should be considered in addition to LDL reduction. 相似文献
28.
van der Steeg WA Hovingh GK Klerkx AH Hutten BA Nootenboom IC Levels JH van Tol A Dallinga-Thie GM Zwinderman AH Kastelein JJ Kuivenhoven JA 《Journal of lipid research》2007,48(3):674-682
It is unclear whether cholesteryl ester transfer protein (CETP) contributes to high density lipoprotein cholesterol (HDL-C) levels in hyperalphalipoproteinemia (HALP) in Caucasians. Moreover, even less is known about the effects of hereditary CETP deficiency in non-Japanese. We studied 95 unrelated Caucasian individuals with HALP. No correlations between CETP concentration or activity and HDL-C were identified. Screening for CETP gene defects led to the identification of heterozygosity for a novel splice site mutation in one individual. Twenty-five heterozygotes for this mutation showed reduced CETP concentration (-40%) and activity (-50%) and a 35% increase of HDL-C compared with family controls. The heterozygotes presented with an isolated high HDL-C, whereas the remaining subjects exhibited a typical high HDL-C/low-triglyceride phenotype. The increase of HDL-C in the CETP-deficient heterozygotes was primarily attributable to increased high density lipoprotein containing apolipoprotein A-I and A-II (LpAI:AII) levels, contrasting with an increase in both high density lipoprotein containing apolipoprotein A-I only and LpAI:AII in the other group. This study suggests the absence of a relationship between CETP and HDL-C levels in Caucasians with HALP. The data furthermore indicate that genetic CETP deficiency is rare among Caucasians and that this disorder presents with a phenotype that is different from that of subjects with HALP who have no mutation in the CETP gene. 相似文献
29.
Background
The analysis of genetic variation in populations of infectious agents may help us understand their epidemiology and evolution. Here we study a model for assessing the levels and patterns of genetic diversity in populations of infectious agents. The population is structured into many small subpopulations, which correspond to their hosts, that are connected according to a specific type of contact network. We considered different types of networks, including fully connected networks and scale free networks, which have been considered as a model that captures some properties of real contact networks. Infectious agents transmit between hosts, through migration, where they grow and mutate until elimination by the host immune system. 相似文献30.
R Moriggi Jr HS Di Mauro SC Dias JM Matos MB Urtado NF Camar?o IV Sousa Neto DC Nascimento RA Tibana CO Assump??o J Prestes CB Urtado 《Biology of sport / Institute of Sport》2015,32(4):289-294
Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 ± 4 years, 74 ± 3 kg, 174 ± 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances. 相似文献