Biomedical subjects

Benoit Lamarche

Publications and source records attributed to Benoit Lamarche.

5 recordsLinked to original sources

PubMed2006

Endothelial lipase: its role in cardiovascular disease.

Endothelial lipase (EL) has recently been identified as a new member of the triglyceride lipase gene family. EL shares a relatively high degree of homology with lipoprotein lipase and hepatic lipase, but it appears to be more specific at hydrolyzing phospholipids than lipoprotein lipase and hepatic lipase. EL is also the only identified lipase that is synthesized and expressed by endothelial cells. Data from in vitro and in vivo animal studies have suggested that EL may play a key role in modulating the metabolism of high density lipoproteins. Data are less consistent in clarifying how EL contributes to the metabolism of apolipoprotein B-containing lipoproteins. Investigations in humans are scarce. To date, increased plasma EL concentrations have been associated with a deteriorated lipoprotein-lipid profile along with elevated plasma triglyceride and apolipoprotein B concentrations, as well as with smaller low density lipoprotein particle size. Elevated proinflammatory cytokine concentrations and an increased prevalence of the metabolic syndrome have also been observed among individuals with elevated plasma EL concentrations. Taken together, data suggest that EL is one of several key regulatory enzymes of lipoprotein-lipid metabolism and that a proinflammatory state, such as the metabolic syndrome, may be implicated in the processes relating plasma EL concentrations and lipoprotein concentrations. EL should thus be considered to play an important role in the pathophysiology of cardiovascular disease.

Animals↗

PubMed2005

Circulating levels of oxidative stress markers and endothelial adhesion molecules in men with abdominal obesity.

CONTEXT: It has been suggested that oxidative stress and endothelial dysfunction could play a role in the higher cardiovascular disease risk noted in the abdominally obese population. OBJECTIVE: The objective of this study was to describe the associations between abdominal fat accumulation, oxidative stress, and endothelial dysfunction in men. DESIGN: A complete physical and metabolic profile was assessed in a group of 56 men covering a wide range of adiposity and plasma oxidized low-density lipoprotein (OxLDL), and soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin, and C-reactive protein concentrations were determined. RESULTS: We found that abdominal visceral adipose tissue was positively associated with plasma OxLDL (r = 0.52; P < 0.0001) and C-reactive protein (r = 0.60; P < 0.0001) concentrations. We also found significant associations between plasma E-selectin levels and hyperinsulinemia (r = 0.39; P < 0.005) as well as with the homeostasis model assessment index of insulin resistance (r = 0.42; P < 0.005). CONCLUSIONS: Our study showed that plasma OxLDL levels and low-grade systemic inflammation are increased in men with a high visceral adipose tissue accumulation. Furthermore, our results support the notion that insulin resistance is associated with endothelial activation. Overall, our observations give us further insights on the increased cardiovascular disease risk frequently noted among viscerally obese, insulin-resistant individuals.

Abdominal Fat↗

PubMed2004

Evidence that hepatic lipase deficiency in humans is not associated with proatherogenic changes in HDL composition and metabolism.

The aim of the present study was to characterize the composition and metabolism of HDL in subjects with complete hepatic lipase (HL) deficiency. Analyses were carried out in three complete and three partial HL-deficient subjects as well as in eight normotriglyceridemic (NTG) and two hypertriglyceridemic controls. Complete HL deficiency was associated with hypertriglyceridemia and with a 3.5-fold increase in HDL-triglyceride (TG) levels. The in vivo kinetics of apolipoprotein A-I (apoA-I) and apoA-II (d < 1.25 g/l) were studied in the fasted state using a primed-constant infusion of l-(5,5,5-D3)leucine for 12 h. Complete HL deficiency was associated with a reduced fractional catabolic rate of apoA-I in the HL-deficient female proband (-47%) and in her two brothers (-21%) compared with gender- and TG-matched controls. Total plasma and HDL from complete HL-deficient patients were able to mediate normal cholesterol efflux from human skin fibroblasts labeled with [3H]cholesterol. Complete HL deficiency was also associated with normal levels of prebeta-migrating apoA-I-containing HDL separated by two-dimensional gel electrophoresis and with an accumulation of large HDL particles compared with NTG controls. These results suggest that HL activity is important for adequate HDL metabolism, although its presence may not be necessary for normal HDL-mediated reverse cholesterol transport.

Apolipoprotein A-I↗

PubMed2003

The T111I mutation in the EL gene modulates the impact of dietary fat on the HDL profile in women.

The objective of the present study was to examine the impact of the T111I missense mutation in exon 3 of the endothelial lipase (EL) gene on HDL and its potential interaction effect with dietary fat. The study sample included 281 women and 216 men aged between 17 and 76 years from the Québec Family Study. Plasma HDL3-C levels of I111I homozygote women were higher compared with those of women carrying the wild-type allele (P = 0.03). These differences were not attenuated when adjusted for levels of obesity and were not observed among men. Dietary PUFA interacted with the T111I mutation to modulate apolipoprotein A-I (apoA-I) and HDL3-C levels among women. Specifically, a diet rich in PUFA was associated with increased apoA-I levels among women carriers of the I111 allele and with decreased apoA-I among women homozygotes for the wild-type allele (P = 0.002). A similar interaction was observed with plasma HDL3-C levels (P = 0.003). These interactions were not observed among men. In conclusion, the EL T111I mutation appears to have a modest effect on plasma HDL levels. The gene-diet interaction among women, however, suggests that the T111I missense mutation may confer protection against the lowering effect of a high dietary PUFA intake on plasma apoA-I and HDL3-C levels.

Adipose Tissue↗

PubMed2002

Hypertriglyceridemic hyperapoB in type 2 diabetes.

OBJECTIVES: Much less attention has been paid to LDL in type 2 diabetes than to VLDL or HDL. In particular, there are few data on apoB levels in these patients. Moreover, most reports have focused on mean lipoprotein levels and consequently there is little information on the frequencies of the various dyslipidemic phenotypes. RESEARCH DESIGN AND METHODS: Plasma and lipoprotein lipids, apoB and apoA1 were measured by standardized methods. LDL particle size was determined by PAGE. The total cohort was divided into phenotypes by two different methods. The first was based on triglycerides (> or = or <1.5 mmol/l) and LDL cholesterol (> or = or <4 mmol/l), whereas the second was based on triglycerides (> or = or <1.5 mmol/l) and apoB (> or = or <120 mg/dl). RESULTS: For the overall cohort, plasma triglycerides were elevated (2.13 +/- 1.6 mmol/l), total and LDL cholesterol were normal (5.34 +/- 1.1 and 3.28 +/- 0.88 mmol/l, respectively), and peak LDL size was reduced (252.9 +/- 5.8 A). HDL cholesterol was between the 25th and 50th percentiles of the general population (1.12 +/- 0.36 mmol/l). The average level of apoB was 114 +/- 29 mg/dl, a value that is between the 50th and 75th percentiles of the general population and is higher than that for LDL cholesterol, which was between the 25th and the 50th percentiles of the population. The results of the phenotyping analysis were as follows. Using the conventional approach, only 23% has abnormal LDL, i.e., an elevated LDL cholesterol level. Using the new approach, almost 40% has an elevated apoB and therefore an elevated LDL particle number. Only 12.8% has combined hyperlipidemia based on the conventional approach, whereas almost one-third had the equivalent, hypertriglyceridemic hyperapoB-based on the new algorithm. The severity of the dyslipoproteinemia in this group was noteworthy. Although the average LDL cholesterol was 3.91 mmol/l, a value just below the 75th percentile of the general population, the average apoB was 145 mg/dl, a value that approximates the 95th percentile of the population. CONCLUSIONS: The dyslipidemic profile of patients with type 2 diabetes is not uniform. A substantial group have normal lipids and normal LDL particle number and size whereas others have markedly abnormal profiles. Diagnosis based on triglycerides and apoB rather than triglycerides and LDL cholesterol revealed that more than one in five had hypertriglyceridemic hyperapoB, which is characterized by hypertriglyceridemia, marked elevation of LDL particle number, small dense LDL, and low HDL, a constellation of abnormalities that is associated with markedly accelerated atherogenesis and therefore justifies intensive medical therapy.

Apolipoproteins↗