Biomedical subjects

E Dusserre

Publications and source records attributed to E Dusserre.

6 recordsLinked to original sources

PubMed1995

Cholesterol ester transfer and high-density lipoprotein conversion in normolipidemic, hypercholesterolemic, and hypertriglyceridemic non-insulin-dependent diabetics.

Non-insulin-dependent diabetes (NIDD) is a situation at elevated risk for atherosclerosis. The plasma concentration of high-density lipoprotein (HDL) is often lowered. This may be accompanied by an abnormal composition and profile of HDL subfractions. These abnormalities might result in part from a defect in the net cholesterol ester transfer (CET) from HDL to apo B-containing lipoproteins. In the present work, we have studied the net CET and HDL conversion in normolipidemic, hypercholesterolemic, and hypertriglyceridemic NIDD, by comparison with control subjects. HDL conversion was determined by gradient gel electrophoresis after 23 h incubation in plasma with HDL3 labeled with a nontransferable synthetic marker. The net CET in normolipidemic NIDD was similar to that of controls, while it was approximately doubled in hypercholesterolemic or hypertriglyceridemic NIDD. In all groups, HDL conversion was comparable, with the exception of hypertriglyceridemic NIDD. In the latter group, the labeled HDL2/HDL3 ratio was increased, indicating a more complete conversion that was correlated with the triglyceride/cholesterol ester ratio in HDL. In addition, when lecithin:cholesterol acyl transferase was inhibited, a distinct peak of small HDL particles appeared in the density range of HDL2 in contrast with the other groups where only small HDL3 was formed. Recombination experiments showed that these abnormalities were attributable to the plasma in which labeled HDL3 was incubated rather than to the origin (control or hypertriglyceridemic NIDD) of labeled HDL3. These data suggest that in NIDD, hypertriglyceridemia may result in abnormalities of HDL conversion due to alterations in HDL composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

PubMed1995

Omega-3 fatty acids in smooth muscle cell phospholipids increase membrane cholesterol efflux.

The aim of our work was to determine whether fatty acid modifications in smooth muscle cell phospholipids affect cholesterol efflux and desorption. [3H]Cholesterol was used to label cholesterol pools in the whole cell or selectively in the plasma membrane. Cells were incubated for 12 h in order to increase oleate, linoleate, arachidonate, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in phospholipids. Cholesterol efflux was monitored using native or tetranitromethane modified high-density lipoprotein3 (HDL3). When all cholesterol pools were labeled, the efflux from cells treated with different fatty acids were not different. Plasma membrane cholesterol efflux remained unchanged after oleate, linoleate or arachidonate treatments, but was markedly increased after EPA and DHA enrichment, both with native HDL3 and with tetranitromethane-high-density lipoprotein. These results suggest that the positive effects of n-3 fatty acid consumption on the atherosclerotic process could be linked in part to an increase in plasma membrane cholesterol efflux from vascular smooth muscle cells.

Animals↗

PubMed1994

Decrease in high density lipoprotein binding sites is associated with decrease in intracellular cholesterol efflux in dedifferentiated aortic smooth muscle cells.

One of the key features of atherosclerosis formation and progression is 'dedifferentiation' of contractile arterial smooth muscle cells (SMC) in synthetic cells. In primary cultures and subcultures before 10 and after 200 passages, SMC exhibit contractile-like, synthetic and transformed phenotypes, respectively, providing a good model for studying dedifferentiation process in vitro: the rationale for comparing these phenotypes of SMC in vivo rests in similar changes in cytoenzymatic and cytoskeletal features. In vivo, dedifferentiated SMC are transformed into foam cells by accumulating lipids. Thus, the aim of this study was to determine whether cholesterol metabolism undergoes changes in dedifferentiated cells and the three cultured phenotypes were compared in regard to their cholesterol efflux mechanisms. Phenotypic changes were shown to be associated with decrease in intracellular cholesterol apoprotein mediated efflux and translocation but also with decrease in high affinity binding sites for native HDL. Thus, the dedifferentiation process triggers a need for increased supply of cholesterol for membrane synthesis and efflux down-regulation mechanisms are aimed at maximizing cholesterol availability to the cell. Plasma membrane cholesterol efflux, which seems to be apoprotein-independent, decrease slightly with cell dedifferentiation suggesting either modifications in the dedifferentiated cell membranes physical properties. Taken together, these different results showed that dedifferentiation of arterial SMC is associated with decrease in the different steps of the efflux process, which could constitute one of the early events in their foam cell transformation.

Animals↗

PubMed1994

High-density lipoprotein 3 stimulates phosphatidylcholine breakdown and sterol translocation in rat aortic smooth muscle cells by a phospholipase C/protein kinase C-dependent process.

The aim of this study was to elucidate signal transduction pathways following high-density lipoprotein 3 (HDL3) fixation to HDL high-affinity binding sites and leading to translocation of newly synthesized cholesterol to the plasma membrane pool for efflux. First, membrane phosphatidylcholine (PC) breakdown and 1,2-diacylglycerol (DAG) production were investigated following HDL3 or tetranitromethane (TNM)-HDL incubation with smooth muscle cells in culture. Second, newly synthesized cholesterol was labeled using [3H] mevalonolactone. Phospholipase C (PLC) and protein kinase C (PKC) were stimulated using carbachol and phorbol 12-myristate 13-acetate. Translocation and efflux of newly synthesized cholesterol were monitored using the cholesterol oxidase method and TNM-HDL as cholesterol acceptor. Results showed that: (1) native HDL3 but not modified HDL was able to stimulate PC breakdown and DAG formation; and (2) PLC and PKC stimulation using specific agents induce cholesterol translocation from intracellular to plasma membrane pool. Taken together, these two sets of results suggest that native HDL3 could induce cholesterol translocation by a PLC/PKC process in smooth muscle cells.

Animals↗

PubMed1993

Lipid biosynthesis in cultured arterial smooth muscle cells is related to their phenotype.

During the atherogenic process in vivo, arterial smooth muscle cells (SMC) undergo changes in their phenotype. In the present study, rat SMC from primary cultures and from subcultures before 10 and after 200 passages, showing contractile-like, synthetic and transformed phenotypes, respectively, were compared in regard to their lipid content and biosynthesis. The rationale for comparing these phenotypes rests in the similar changes in phenotype of SMC that occur in the formation and progression of atherosclerotic lesions. Phenotype changes were shown to be associated with changes in the phospholipid content of SMC. Phospholipid levels increased, but not as significantly as did cholesterol levels when passing from contractile to synthetic and transformed cells (1.23 +/- 0.18, 2.28 +/- 0.26 and 3.25 +/- 0.23 micrograms/10(6) cells, respectively). Cholesterol normalized in respect to cell protein was increased to the same extent. Lipid synthesis as judged by [14C]acetate incorporation was increased 3- to 12-fold in the synthetic and transformed cells, respectively, compared to contractile cells. After thin-layer chromatography, radioactivity was shown to be markedly increased in most of the lipid fractions, but label in the cholesterol fraction of synthetic and transformed cells was increased by 7- and 21-fold, respectively. Thus, SMC in vitro were shown to drastically increase cholesterol biosynthesis associated with phenotype changes. Such changes are known to occur in vivo and might represent a critical step in the deposition of excess cholesterol within foam cells.

Animals↗

PubMed1991

[Modulation of arterial smooth muscle cells in culture and cholesterol exchange].

The phenotypic modulation and the enhanced proliferation of smooth muscle cells (SMC) as well as their foam transformation are major processes in arterial pathophysiology and during atherogenesis. Arterial SMC play a crucial role, in response to several stimuli: the SMC "activation" is an essential condition leading to the adult atherosclerotic plaque formation. Owing to the difficulty to study the SMC regulation in vivo, most of the literature in this field refers to in vitro models. Modulated SMC in culture, changing from a contractile to a synthetic state, share similar features with atherosclerotic plaques cells. The phenotypic modulation of SMC is expressed by morphological, biochemical, metabolic and functional modifications. The regulation of cholesterol movements might influence the foam transformation process of arterial SMC.

Animals↗