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Biomedical subjects

B A Griffin

Publications and source records attributed to B A Griffin.

At least 19 recordsLinked to original sources
PubMed2001

The effect of n-3 fatty acids on low density lipoprotein subfractions.

A predominance of small, dense low density lipoprotein (LDL) represents a significant source of increased risk for the development of coronary heart disease in Westernized countries. Dietary long-chain n-3 polyunsaturated fatty acids exert a potent triglyceride-lowering effect that redistributes LDL subfractions toward larger and lighter particles. These dietary fatty acids thus have a key role to play in providing protection against this particularly atherogenic type of LDL.

Apolipoproteins E↗
PubMed2001

Postprandial lipid handling.

The etiological importance of postprandial lipid metabolism in the development of coronary artery disease is now well established. Since then, the work of Patsch and others has helped to establish the etiological importance of postprandial lipid metabolism in the development of coronary artery disease. Dietary and pharmacological interventions have been shown to produce dramatic improvement in postprandial lipid handling in high risk groups and have potential to prevent coronary artery disease through these effects. Research effort continues to focus on the complex mechanisms which underlie defects in postprandial lipid handling, with a view to understanding how lifestyle variables such as diet can be modified to prevent coronary artery disease.

Apolipoproteins E↗
PubMed2000

Lack of association between lipaemia and central adiposity in subjects with an atherogenic lipoprotein phenotype (ALP).

OBJECTIVE: To investigate the associations between indices of adiposity and cardiovascular risk factors in individuals with an atherogenic lipoprotein phenotype (ALP). SUBJECTS: Fifty-five men, aged 34-69 y, body mass index (BMI) 22-35 kg/m2, with an ALP lipid profile (triglycerides (TG) 1.5-4.0 mmol/l, HDL<1.1 mmol/l; %LDL-3>40% total LDL). DESIGN: Each participant provided a fasting blood sample and underwent an 8 h postprandial assessment and had anthropometric measurements taken. OUTCOME MEASURES: BMI, waist circumference (W), waist-to-hip ratio (W/H), sum of skinfolds (SSK), fasting and postprandial concentrations of glucose, insulin and plasma lipids, post-heparin lipase activity, and apoE genotype. RESULTS: The expected positive associations between BMI, W and SSK and fasting and postprandial insulin were observed (r=0.42-0.65). Little association between glucose responses and any measures of adiposity was evident. Unexpectedly, there were no positive associations between measures of central adiposity (W and W/H) and fasting and postprandial TG responses, with a trend towards negative associations in this study group (TG AUC vs W, r=-0.23, P=0.097; TG IAUC vs W/H, r=-0.26, P=0.068). Subgroup analysis indicated that lack of a positive association between central adiposity and postprandial TG values was more evident in those with one E4 allele (r=-0.42, P=0.077) relative to non-E4 carriers (r=-0.16, P=0.430). The expected positive associations between insulin and TG responses were not observed (r=-0.03 to -0.36). CONCLUSION: In this ALP group the expected positive association between TG responses and a centralized distribution of body fat was not observed, particularly in individuals with an apoE4 genotype. Our findings are not in line with the view that there is a clear causal relationship between insulin resistance and the lipid abnormalities associated with ALP.

Abdomen↗
PubMed2000

ApoE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype.

The study assessed the efficacy of fish oil supplementation in counteracting the classic dyslipidemia of the atherogenic lipoprotein phenotype (ALP). In addition, the impact of the common apolipoprotein E (apoE) polymorphism on the fasting and postprandial lipid profile and on responsiveness to the dietary intervention was established. Fifty-five ALP males (aged 34 to 69 years, body mass index 22 to 35 kg/m(2), triglyceride [TG] levels 1.5 to 4.0 mmol/L, high density lipoprotein cholesterol [HDL-C] <1.1 mmol/l, and percent low density lipoprotein [LDL]-3 >40% total LDL) completed a randomized placebo-controlled crossover trial of fish oil (3.0 g eicosapentaenoic acid/docosahexaenoic acid per day) and placebo (olive oil) capsules with the 6-week treatment arms separated by a 12-week washout period. In addition to fasting blood samples, at the end of each intervention arm, a postprandial assessment of lipid metabolism was carried out. Fish oil supplementation resulted in a reduction in fasting TG level of 35% (P<0.001), in postprandial TG response of 26% (TG area under the curve, P<0.001), and in percent LDL-3 of 26% (P<0.05). However, no change in HDL-C levels was evident (P=0.752). ANCOVA showed that baseline HDL-C levels were significantly lower in apoE4 carriers (P=0.035). The apoE genotype also had a striking impact on lipid responses to fish oil intervention. Individuals with an apoE2 allele displayed a marked reduction in postprandial incremental TG response (TG incremental area under the curve, P=0.023) and a trend toward an increase in lipoprotein lipase activity relative to non-E2 carriers. In apoE4 individuals, a significant increase in total cholesterol and a trend toward a reduction in HDL-C relative to the common homozygous E3/E3 profile was evident. Our data demonstrate the efficacy of fish oil fatty acids in counteracting the proatherogenic lipid profile of the ALP but also that the apoE genotype influences responsiveness to this dietary treatment.

Adult↗
PubMed1999

Lipoprotein atherogenicity: an overview of current mechanisms.

Raised serum cholesterol does not adequately explain the increased risk of CHD within populations or the relationship between diet and CHD. Nevertheless, the principal transport vehicle of cholesterol in the circulation, LDL, must still be regarded as the most atherogenic lipoprotein species, but not because of its contribution to serum cholesterol. The atherogenic potential of LDL in the majority of individuals arises from an increase in the number of small dense LDL particles and not from its cholesterol content per se. There is now a wealth of evidence from cross-sectional and prospective studies to show that LDL particle size is significantly associated with CHD and predictive of increased coronary risk. Moreover, there are a number of credible mechanisms to link small dense LDL with the atherogenic process. The rate of influx of serum lipoproteins into the arterial wall is a function of particle size, and will thus be more rapid for small dense LDL. Components of the extracellular tissue matrix in the intima, most notably proteoglycans, selectively bind small dense LDL with high affinity, sequestering this lipoprotein in a pro-oxidative environment. The oxidation of LDL promotes the final deposition of cholesterol in the arterial wall, and numerous studies have shown small dense LDL to be more susceptible to oxidative modification than its larger and lighter counterparts. An increase in the number of small dense LDL particles may originate from a defect in the metabolism of triacylglycerol-rich lipoproteins. One mechanism may involve the overproduction and increased residence time of large triacylglycerol-rich VLDL in the postprandial phase, a situation thought to arise through pathways of insulin resistance.

Arteriosclerosis↗
PubMed1999

Inter-relationships between small, dense low-density lipoprotein (LDL), plasma triacylglycerol and LDL apoprotein B in an atherogenic lipoprotein phenotype in free-living subjects.

A predominance of small, dense low-density lipoprotein (LDL) is a major component of an atherogenic lipoprotein phenotype, and a common, but modifiable, source of increased risk for coronary heart disease in the free-living population. While much of the atherogenicity of small, dense LDL is known to arise from its structural properties, the extent to which an increase in the number of small, dense LDL particles (hyper-apoprotein B) contributes to this risk of coronary heart disease is currently unknown. This study reports a method for the recruitment of free-living individuals with an atherogenic lipoprotein phenotype for a fish-oil intervention trial, and critically evaluates the relationship between LDL particle number and the predominance of small, dense LDL. In this group, volunteers were selected through local general practices on the basis of a moderately raised plasma triacylglycerol (triglyceride) level (>1.5 mmol/l) and a low concentration of high-density-lipoprotein cholesterol (<1.1 mmol/l). The screening of LDL subclasses revealed a predominance of small, dense LDL (LDL subclass pattern B) in 62% of the cohort. As expected, subjects with LDL subclass pattern B were characterized by higher plasma triacylglycerol and lower high-density lipoprotein cholesterol (<1.1 mmol/l) levels and, less predictably, by lower LDL cholesterol and apoprotein B levels (P<0.05; LDL subclass A compared with subclass B). While hyper-apoprotein B was detected in only five subjects, the relative percentage of small, dense LDL-III in subjects with subclass B showed an inverse relationship with LDL apoprotein B (r=-0.57; P<0.001), identifying a subset of individuals with plasma triacylglycerol above 2.5 mmol/l and a low concentration of LDL almost exclusively in a small and dense form. These findings indicate that a predominance of small, dense LDL and hyper-apoprotein B do not always co-exist in free-living groups. Moreover, if coronary risk increases with increasing LDL particle number, these results imply that the risk arising from a predominance of small, dense LDL may actually be reduced in certain cases when plasma triacylglycerol exceeds 2.5 mmol/l.

Adult↗
PubMed1998

Specific covalent labeling of recombinant protein molecules inside live cells.

Recombinant proteins containing four cysteines at the i, i + 1, i + 4, and i + 5 positions of an alpha helix were fluorescently labeled in living cells by extracellular administration of 4',5'-bis(1,3, 2-dithioarsolan-2-yl)fluorescein. This designed small ligand is membrane-permeant and nonfluorescent until it binds with high affinity and specificity to the tetracysteine domain. Such in situ labeling adds much less mass than does green fluorescent protein and offers greater versatility in attachment sites as well as potential spectroscopic and chemical properties. This system provides a recipe for slightly modifying a target protein so that it can be singled out from the many other proteins inside live cells and fluorescently stained by small nonfluorescent dye molecules added from outside the cells.

Amino Acid Sequence↗
PubMed1998

The effect of smoking on post-heparin lipoprotein and hepatic lipase, cholesteryl ester transfer protein and lecithin:cholesterol acyl transferase activities in human plasma.

INTRODUCTION: Smoking is associated with dyslipidaemia, particularly raised plasma triglycerides and reduced high-density lipoprotein (HDL)-cholesterol and a delayed clearance of triglyceride in fat tolerance tests. The aim of this study was to investigate whether these phenomena could be explained by a reduced lipoprotein lipase activity in smokers. METHODS: A group of 40 healthy individuals [plasma cholesterol 5.07 (SD 0.90) mmol L-1, plasma triglyceride 1.02 (SD 0.39) mmol L-1)] was studied to examine the effects of smoking on plasma enzyme activities, particularly post-heparin lipase activities. The group comprised 20 smokers and 20 non-smokers, who were matched for age, gender and body mass index (BMI). RESULTS: Post-heparin lipoprotein lipase (LPL) activity [3.89 (SD 1.58) vs. 5.85 (SD 2.30) mumol free fatty acids (FFA) mL-1 h-1, P < 0.005], but not post-heparin hepatic lipase (HL) activity, was reduced in smokers. Plasma cholesteryl ester transfer protein (CETP) activity and lecithin: cholesterol acyl transferase (LCAT) activity were measured in a subgroup of 18 individuals, comprising nine smokers with nine matched non-smokers. There was no difference in CETP activities between two groups, but smokers had a significantly reduced plasma LCAT activity [112 (SD 23) vs. 152 (SD 24) nmol cholesterol mL-1 h-1, P < 0.005]. In both smokers (r=-0.53, P < 0.05) and non-smokers (r=-0.54, P < 0.05), HDL2 concentration was negatively associated with HL activity. In non-smokers, HDL3 concentration was negatively associated with CETP activity (r= -0.77, P < 0.05), whereas in smokers HDL3 concentration was negatively associated with LCAT activity (r= -0.78, P < 0.050). CONCLUSION: It was shown by direct measurement that the activity of plasma post-heparin LPL is reduced in smokers, independently of age, gender and BMI. It is concluded that this enzyme perturbation associated with smoking may contribute to the development of the atherogenic lipoprotein phenotype seen in smokers.

Adult↗
PubMed1998

Consumption of red wine polyphenols reduces the susceptibility of low-density lipoproteins to oxidation in vivo.

Red wine polyphenols (RWPPs) were obtained from red wine by absorption and elution from a resin column. Red wine (375 mL/d), white wine (375 mL/d), RWPPs (1 g/d, equivalent to 375 mL red wine/d) in capsules, RWPPs (1 g/d) dissolved in white wine, or a control alcoholic drink (40 g ethanol/d) was given to groups of 6-9 healthy men for 2 wk. Plasma LDL was separated by ultracentrifugation and desalted by dialyzing against a phosphate buffer without EDTA. In the copper-catalyzed peroxidation of LDL (copper-diene assay), the mean lag time increased by 17.8 min after red wine, 14.2 min after RWPP capsules, and 11.7 min after RWPPs in white wine. These groups also showed decreases in thiobarbituric acid-reactive substances, lipid peroxides, and conjugated dienes and increases in plasma and LDL polyphenols. The only change with white wine was an increase in thiobarbituric acid-reactive substances; there were no changes after the control drink. In a second study, RWPPs (1 and 2 g/d) and vitamin E [1000 IU (671 mg)/d] were given for 2 wk. In the copper-diene assay the addition of 10 micromol EDTA/L abolished the increased lag time of 17.7 min seen with 1 g RWPP/d and changed the increased lag time from 13.2 to 4.5 min seen with 2 g RWPP/d. Vitamin E increased lag time by 67.6 min with dialysis without EDTA and by 50.5 min with EDTA. When the column method was used for desalting LDL, all 3 treatments produced an increase in lag time. The failure of some authors to obtain antioxidant effects with the consumption of red wine may be due to the differing techniques.

Adult↗
PubMed1996

Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans.

Low density lipoprotein (LDL) is known to bind to arterial wall proteoglycans (APG), an interaction which may initiate cholesterol deposition in the arterial wall. The objective of this study was to determine whether a predominance of small, dense LDL (LDL-III, d = 1.044-1.063 g/ml) in the circulation in association with an atherogenic lipoprotein phenotype (ALP) (i.e. LDL-III > 100 mg/dl, an elevated plasma triglyceride and a low high density lipoprotein cholesterol) alters LDL reactivity towards APG. Total LDL (d = 1.019-1.063 g/ml) was isolated from 59 patients undergoing coronary angiography (39 males and 20 females) and the LDL subfraction profile determined by non-equilibrium density gradient centrifugation. A binding assay was developed in which total LDL (0.1 mg/ml apo LDL) was mixed with a standard preparation of APG containing 2.5 micrograms/ml chondroitin sulphate and the extent of APG-LDL complex formation followed by absorbance measurement and the amount of precipitated LDL cholesterol. APG-LDL complex formation was positively associated with (a) the percentage of LDL-III within total LDL (r = 0.48, P < 0.0001); (b) the plasma triglyceride level (r = 0.27, P < 0.04); and negatively associated with (a) the percentage of the buoyant LDL-I (d = 1.019-1.033 g/ml)(r = -0.47, P < 0.0001); and (b) the HDL cholesterol concentration (r = -0.37, P < 0.004). There was no association with the percentage of the major LDL species LDL-II. When the patients were divided according to the presence or absence of an ALP i.e. LDL-III greater or less than 100 mg/dl respectively, proteoglycan-LDL complex formation was significantly higher in the former compared to the latter group of patients (P < 0.0001). This study therefore provides evidence that the extent of the interaction of LDL with APG varies considerably between individuals and is enhanced in the presence of ALP. It is postulated that the increased atherogenicity associated with ALP may in part be due to prolonged and enhanced retention of LDL by the arterial wall.

Aged↗
PubMed1996

Effects of colestipol alone and in combination with simvastatin on apolipoprotein B metabolism.

The effects of colestipol therapy alone (20 g/d) or combined with simvastatin (20 mg/d) were examined in a group of eight male patients with primary moderate hypercholesterolemia (total cholesterol > or = 6.5 mmol/L [> or = 250 mg/dL]) who had undergone coronary artery bypass grafting more than 3 months previously. Colestipol therapy decreased total cholesterol by 14% (P < .001) and LDL cholesterol (LDL-C) by 23% (P < .001), while dual therapy decreased total cholesterol by 38% and LDL-C by 52% (both P < .001 versus baseline). No significant changes were observed in plasma triglyceride, VLDL cholesterol, or HDL cholesterol levels. VLDL subfraction turnovers were conducted at baseline and again on each regimen. ApoB kinetic parameters derived from a multicompartmental model suggested that colestipol therapy resulted in an expansion of the total VLDL apoB pool (36%, P < .05) that was largely due to a fall in the clearance rate of VLDL1 apoB (49%), while the LDL apoB pool decreased 23% as a result of diminished direct LDL input. The model used also revealed that addition of simvastatin to the resin therapy caused increases in the fractional transfer rates of VLDL2 to IDL and IDL to LDL together with a 37% increment in the LDL apoB fractional catabolic rate. Compared with baseline, combined therapy generated falls in both IDL (35%, P = .01) and LDL (37%, P < .04) apoB pools due to enhanced clearance of IDL (214%, P < .03) and reduced total input of LDL (39%, P < .003).

Adult↗