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Biomedical subjects

N Savion

Publications and source records attributed to N Savion.

At least 55 records · Page 3Linked to original sources
PubMed1996

The nuclear trafficking of extracellular fibroblast growth factor (FGF)-1 correlates with the perinuclear association of the FGF receptor-1alpha isoforms but not the FGF receptor-1beta isoforms.

The alternatively spliced fibroblast growth factor receptor (FGFR)-1 isoforms, FGFR-1alpha and FGFR-1beta, are characterized by the presence of either three or two Ig-like loops in the extracellular domain and are differentially expressed during embryonic development and tumor progression. We have previously shown that in cells irreversibly committed to DNA synthesis by FGF-1, approximately 15% of cell surface FGFR-1 traffics to a perinuclear locale as a structurally intact and functional tyrosine kinase (Prudovsky, I., Savion, N., Zhan, X., Friesel, R., Xu, J., Hou, J., McKeehan, W. L., and Maciag, T. (1994) J. Biol. Chem. 269, 31720-31724). In order to define the structural requirement for association of FGFR-1 with the nucleus, the expression and trafficking of FGFR-1 in FGFR-1alpha and FGFR-1beta L6 myoblast transfectants was studied. Although FGFR-1alpha was expressed as p145 and p125 forms, FGFR-1beta was expressed as p120 and p100 forms in the L6 myoblast transfectants. Tunicamycin and N-glyconase experiments suggest that these forms of FGFR-1alpha and FGFR-1beta are the result of differential glycosylation. However, only the p145 form of FGFR-1alpha and the p120 form of FGFR-1beta were able to bind FGF-1 and activate tyrosine phosphorylation. Pulse-chase analysis of FGFR-1 biosynthesis suggests that the p125 and p100 proteins are the precursor forms of p145 FGFR-1alpha and p120 FGFR-1beta, respectively. Because ligand-chase analysis demonstrated that FGFR-1beta L6 myoblast transfectants exhibited a reduced efficiency of nuclear translocation of exogenous FGF-1 when compared with FGFR-1alpha transfectants, the intracellular trafficking of the FGFR-1alpha and FGFR-1beta isoforms was studied using an in vitro kinase assay to amplify immunoprecipitated FGFR-1. Indeed, the appearance of the FGFR-1alpha but not FGFR-1beta isoform in the nuclear fraction of L6 myoblast transfectants suggests that the distal Ig-like loop in FGFR-1alpha mediates the differential nuclear association of FGFR-1alpha as a structurally intact and functional tyrosine kinase. Further, the FGFR-1beta L6 myoblast transfectants but not the FGFR-1alpha myoblast transfectants exhibited a pronounced morphologic change in response to exogenous FGF-1. Because this phenotype change involves the induction of a rounded cellular shape, it is possible that the FGFR-1alpha and FGFR-1beta may ultimately exhibit differential trafficking to adhesion sites.

Alternative Splicing↗
PubMed1996

Metastasis-related cell functions in primary and metastatic tumor cells of AKR lymphoma.

The metastatic phenotype is of extreme complexity. To complete all the stages of metastasis, the tumor cell must possess a whole series of functional abilities. Multiple biological markers are therefore needed to achieve a deeper understanding of the metastatic phenotype. In the present study we compared primary (PT) to metastatic tumor (MT) cells of two AKR lymphoma variants with respect to several cellular functions relevant to various steps of tumor dissemination. The MT cells of the TAU-44 variant had a higher capacity than the PT cells to attach to endothelial monolayers and ECM, exhibited a more elevated motility and a higher capacity to grow in the spleen as a metastatic target organ. However, the TAU-44-MT cells had a lower ability to grow in the kidney than the PT cells. The TAU-33-MT cells had a higher ability to attach to endothelial cells and to grow in both spleen and kidney but were less motile compared to PT cells. Metastatic cells showed, on the whole, higher ability to perform in most, but not all, stage-specific models than primary tumor cells.

Animals↗
PubMed1996

Moderation of herpetic stromal keratitis by basic fibroblast growth factor.

The effect of basic fibroblast growth factor (bFGF) on the evolution of herpes simplex virus (HSV) infection in eyes of rabbits was investigated. Rabbit eyes were infected with HSV-1 by a non-invasive inoculation and treated for 7 days with an eye drop solution containing either bovine bFGF (50 ng; three times daily), or bFGF diluent as control. The treatment started 2 hr, 24 hr or 96 hr post-inoculation (p.i.). Follow-up of clinical disease parameters, such as conjunctivitis, epithelial keratitis, stromal disease, corneal neovascularization and of viral isolation continued for 17 days. The most significant difference between bFGF and control treatments was observed in the development of stromal keratitis. The incidence of stromal disease in the bFGF treated group (2/16 eyes) was significantly lower than in the control group (11/12 eyes) (P = 0.0001), when bFGF was administered 2 hr or 24 hr p.i. The severity of the disease developed in the bFGF treated eyes was also milder than in the control eyes (determined by serial slit-lamp clinical examinations and by histologic sections). Such effect was not demonstrated if the treatment started 96 hr p.i. The same duration of viral shedding was obtained with bFGF treated eyes (2 hr, 24 hr, or 96 hr p.i.) and control eyes. Neither HSV-1-infected, nor sham-inoculated bFGF-treated eyes demonstrated increased neovascularization of the cornea, as compared with the corresponding vehicle-treated control eyes. This study demonstrates that bFGF treatment (starting 2-24 hr p.i.) decreased the occurrence and severity of herpetic stromal keratitis, without subsequent aggravation of corneal vascularization. This beneficial anti-inflammatory effect of bFGF may have future application in the treatment of the most devastating stage of herpetic corneal infection.

Animals↗
PubMed1996

Role of blood components in ocular silicone oil emulsification. Studies on an in vitro model.

PURPOSE: To develop an in vitro model for silicone oil emulsification and to explore the blood components involved in this process. METHODS: The capacity of various blood components to support silicone oil (1000 CS) emulsification was studied by applying 0.5 ml oil on top of 0.5 ml saline containing various blood components. Each tube was sonicated for 150 seconds and centrifuged at 5000 g for 20 minutes. Three phases were noted in the tube: At the top was clear silicone oil, in the middle was emulsified silicone oil, and at the bottom was aqueous solution. The tubes were photographed, and the percentage of the phase length containing emulsified silicone oil (middle) of the total length of the three phases was calculated from the projected image of each tube. RESULTS: Emulsified silicone oil in plasma or serum was initiated after 100 seconds of sonication and quickly reached maximum (approximately 80%) at 120 seconds. The size of these oil droplets prepared in vitro was 0.0467 +/- 0.028 mm, closely resembling that observed in oil samples removed from a patient's anterior chamber (0.038 +/- 0.018 mm). Under these conditions, silicone oil emulsified in the presence of whole blood cells occurred only at a concentration of 120 micrograms protein/ml; in the presence of red blood cell membranes, it occurred at a concentration of 60 micrograms protein/ml. Lipoprotein-deficient serum failed to support emulsification; however, samples of high-density lipoprotein and low-density lipoprotein supported this process. Purified high-density lipoprotein-apolipoproteins supported oil emulsification. The addition of phosphatidylcholine further enhanced this process, but phosphatidylcholine alone failed to support emulsification. CONCLUSIONS: A simple and fast in vitro model to study factors affecting silicone oil emulsification was developed. Using this model, red blood cell membranes, plasma lipoproteins, and purified HDL-apolipoproteins supported silicone oil emulsification. Lipids did not, but they had the capacity to enhance the apolipoprotein-supported emulsification.

Blood Cells↗
PubMed1996

Metastatic potential and multidrug resistance correlation in the B16 melanoma system.

The question of whether metastatic potential and drug resistance are related phenotypes was addressed by comparing the biological behavior of the parental B16 melanoma and a multidrug resistant variant derived from it, the B16/Col/R. A more pronounced metastatic spread to lungs was observed in mice inoculated i.v. with the B16/Col/R variant than in those bearing the parental line. In addition, in the mice injected with the drug resistant melanoma, unusual tumor masses were observed. Large abdominal and spinal cord growths were seen with the MDR variant but not encountered in mice inoculated with the original B16 melanoma. We further attempted to test the capacity of the two cell types to perform several cellular functions relevant to the metastatic process. The B16/Col/R cells displayed a higher aggregability and cell motility than did the B16 cells. Adherence to endothelial cells was higher in the parental line than in the B16/Col/R, possibly supporting a more efficient extravasation of the variant cells. The drug resistant variant displayed a higher capacity to grow locally in kidney, spleen, cecum and peritoneum, as compared to the parental melanoma, indicating a higher ability of homing and growth in these potential target organs for metastasis. A correlation between metastatic potential and multidrug resistance appears therefore to exist in the system examined.

Animals↗
PubMed1995

Aprotinin improves hemostasis after cardiopulmonary bypass better than single-donor platelet concentrate.

Platelet transfusion and aprotinin administration improve platelet function and clinical hemostasis after extracorporeal circulation. To compare two methods of improving postoperative hemostasis, we preoperatively randomized 40 patients undergoing various open heart procedures into two groups. Group A included 20 patients who, immediately after bypass, received single-donor plateletpheresis concentrates collected from ABO-compatible donors (Baxter Autopheresis-C System). They were compared with 20 patients who received high-dose aprotinin (6 x 10(6) KIU) before and during cardiopulmonary bypass (group B). Group A patients showed significantly higher platelet count after single-donor plateletpheresis concentrate transfusion (157 +/- 36 x 10(9)/L compared with 118 +/- 42 x 10(9)/L (p < 0.05). However, platelet aggregation on extracellular matrix was better in group B (3.4 +/- 0.7 versus 2.8 +/- 0.9; p < 0.05). Total 24-hour blood loss and exposure to homologous blood products were significantly less in group B (396 +/- 125 mL and 1.1 +/- 1.6 units compared with 617 +/- 233 mL and 5.4 +/- 3.4 units; p < 0.01). Despite higher platelet count in patients after single-donor plateletpheresis concentrates transfusion, hemostasis in patients receiving aprotinin is better due to improved platelet function.

Aprotinin↗
PubMed1995

Irradiation of fresh whole blood for prevention of transfusion-associated graft-versus-host disease does not impair platelet function and clinical hemostasis after open heart surgery.

Since our previous studies suggested that the transfusion of 1 unit fresh whole blood (FWB) after cardiopulmonary bypass (CPB) using a bubble oxygenator may provide hemostatic benefit equivalent to 8-10 units of platelet concentrates, we have routinely used FWB at the termination of CPB. Two patients who received FWB and developed transfusion-associated graft-versus-host disease (TA-GVHD) prompted us to investigate the effect of irradiation of FWB on platelet and clinical hemostasis. Twenty-four patients were randomized to receive either 1 unit FWB (12 patients), or 1 unit irradiated FWB (IrFWB, 1,500 cGy,12 patients) after CPB. Platelet aggregation on extracellular matrix, studied by a scanning electron microscope and graded from 1 to 4 (from poor to excellent aggregation), was similar in both groups preoperatively [3.3 +/- 0.9 (FWB) and 3.5 +/- 0.5 (Ir FWB)], and at the end of CPB [1.8 +/- 1.2 (FWB) and 1.9 +/- 0.9 (IrFWB)]. Platelet aggregation was similar after transfusion of FWB (3.0 +/- 1.0) and after IrFWB (3.2 +/- 0.8), as was the increase in platelet count. Twenty-four hours total postoperative bleeding was similar (560 +/- 420 and 523 +/- 236 ml for FWB and IrFWB, respectively). We conclude that irradiation of FWB for prevention of TA-GVHD does not impair platelet aggregating capacity, and can be used when blood is donated by the patient's next of kin.

Aged↗
PubMed1995

Specific cementum attachment protein enhances selectively the attachment and migration of periodontal cells to root surfaces.

A specific cementum attachment protein (CAP) was identified in human cementum and found to bind with high affinity to non-demineralized root surfaces, hydroxyapatite and fibronectin. Attempting to elucidate the biological function of this protein and its possible role in cementogenesis the capacity of CAP to promote selective cell migration towards and attachment of various periodontal derived cell populations to root surfaces in vitro was assessed. Human gingival fibroblasts (HGF), periodontal ligament cells (HPC), and alveolar bone cells (HABC) were labeled with [3H]Thymidine during their exponential growth phase. Root slices, 300 microns thick, were incubated with increasing concentrations of CAP. Untreated and fibronectin (FN) treated root slices served as negative and positive controls, respectively. Migration was assessed by placing root slices on confluent layers of labeled cells maintained in serum free medium and determining the number of cells migrated onto the root surface 3 days thereafter. Attachment was assessed by incubating root slices with labeled cell suspensions for 2 h and determining the number of attached cells. CAP promoted both cell migration and attachment dose dependently. HABC responded better than HPC and HGF to CAP treated root slices, and HPC response was higher than that of HGF. Cell attachment was dose dependently inhibited by synthetic RGD peptides. FN did not affect the migration of HGF, barely enhanced that of HABC, and was less potent than CAP at enhancing the migration of HPC. FN was more effective than CAP in promoting the attachment of HGF to root slices, but it was as potent as CAP in supporting the attachment of HPC and HABC.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Process↗
PubMed1995

Metastasis-associated cell functions in AKR lymphoma malignancy variants.

Multiple structural and functional cell properties are responsible for the complex phenotype of the metastatic cell. Cells derived from AKR lymphoma malignancy variants were compared with regard to several cellular functions relevant to the metastatic behavior. Metastatic behavior correlated with relevant in vitro cell activities, such as cell motility, homotypic and heterotypic adhesion as well as proteolytic activity. The Variant displaying the highest degree of malignancy, TAU-42, exhibited the most elevated ability to perform almost each of the cell functions examined: motility, aggregability, capacity to adhere to endothelium and extracellular matrix, heparanase and protease activity and ability to grow in the spleen. The TAU-33 variant was second in rank in the performance of the above activities. The TAU-44 variant cells, the third in rank of malignancy, displayed some peculiar functional behavior: while manifesting the lowest homotypic adherence and heparanase activity, they had a high predilection for growth in kidney.

Animals↗
PubMed1994

Intact and functional fibroblast growth factor (FGF) receptor-1 trafficks near the nucleus in response to FGF-1.

Exogenous fibroblast growth factor-1 (FGF-1) associates with the nucleus in a receptor-dependent manner during the entire G1 period of the BALB/c 3T3 cell cycle (Zhan, X., Hu, X., Friesel, R., and Maciag, T. (1993) J. Biol. Chem. 268, 9611-9620). To further study the role of the FGF receptor (FGFR) during this translocation, the intracellular fate of FGFR-1 protein and enzymatic activity was examined. Immunoprecipitation using multiple FGFR-1 antibodies followed by an in vitro tyrosine kinase activity assay enabled us to identify FGFR-1 as a 130-kDa phosphotyrosine-containing protein associated with the nuclear fraction of NIH 3T3 cells exposed to FGF-1. While FGFR-1 tyrosine kinase activity could be detected as a nuclear-associated protein after a 2-h exposure of the NIH 3T3 cells to FGF-1, this activity appeared to be maximal in the nuclear fraction between 4 and 12 h after FGF-1 treatment. In addition, analysis by confocal immunofluorescence microscopy of quiescent and FGF-1-stimulated NIH 3T3 cells reveal a prominent perinuclear FGFR-1 staining pattern in the cells exposed to FGF-1 but not in the quiescent population. We also observed FGFR-1 associated with the nuclear fraction in FGFR-1-transfected L6 rat myoblasts, which are known to be refractive to exogenous FGF-1 and express relatively low levels of endogenous FGFR-1. In addition, these cells also exhibited the presence of a 145-kDa phosphoprotein in the nuclear fraction that was recognized by FGFR-1 antibodies. These results suggest that the FGFR-1 may be translocated near the nucleus upon interaction with its ligand during the entire G1 period of the NIH 3T3 cell cycle as a structurally intact and functional tyrosine kinase that may be accessible to perinuclear polypeptides as a regulatory enzyme.

3T3 Cells↗
PubMed1993

Inhibition of integrin-mediated platelet aggregation, fibrinogen-binding, and interactions with extracellular matrix by nonpeptidic mimetics of Arg-Gly-Asp.

The interaction of the activated platelet integrin, glycoprotein IIb-IIIa (GPIIb-IIIa) with fibrinogen and von-Willebrand factor (vWF) is essential for platelet aggregation. The minimal structure required for this integrin's binding to fibrinogen is the Arg-Gly-Asp (RGD) sequence. Inasmuch as normal level of GPIIb-IIIa-RGD interactions are required for maintaining hemostasis, elevated platelet aggregation can cause adverse pathological effects. We have previously reported that nonpeptidic mimetics of RGD, consisting of carboxylate and guanidinium groups of Asp and Arg divided by a linear 11-atom spacer, acquired a significant affinity for the GPIIb-IIIa integrin and inhibited platelet aggregation. The structural requirements for the interactions of the RGD sequence with GPIIb-IIIa and the inhibitory potential of a newly designed series of mimetics on platelet aggregation and interactions with extracellular matrix (ECM) were assayed herein. Adenosine-diphosphate (ADP)-induced platelet aggregation was inhibited in a dose-dependent manner by various RGD mimetics, with a maximal inhibition of 80-100% with an IC50 of 3 microM for the most potent inhibitor, NS-11, in which a six-membered ring was introduced into the spacer chain, which exceeded the IC50 attained with the original RGDS peptide. The inhibitory effect of the RGD mimetics was attributed to their specific interaction with the GPIIb-IIIa integrin, since these mimetics inhibited the binding of the PAC-1 mAb to GPIIb-IIIA. Furthermore, the binding of 125I-labeled fibrinogen to platelets was inhibited by the RGD surrogates in a dose-dependent and saturable manner. The RGD-mimetics also inhibited up to 70% the adhesion, aggregation, and deposition of platelets onto ECM.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Platelet aggregation on extracellular matrix: effect of a recombinant GPIb-binding fragment of von Willebrand factor.

Platelets in whole blood incubated on extracellular matrix (ECM) produced by bovine corneal endothelial cells under oscillatory flow conditions demonstrate extensive aggregate formation. Since both platelet-subendothelium and platelet-platelet interactions are mediated by von Willebrand factor (vWF), we used this system to examine the effect of a recombinant GPIb-binding fragment of vWF (designated RG12986), comprising residues 445-733 of the native vWF subunit, on platelet reactivity with ECM. The seven cysteines present in the RG12986 fragment were reduced and alkylated in order to achieve a monomeric conformation. The recombinant vWF fragment binds to unstimulated platelets in the absence of exogenous modulators. When added to platelet-rich plasma, it inhibits ristocetin-induced platelet agglutination. Binding of 51Cr-labeled platelets in reconstituted whole blood to ECM was inhibited by RG12986 in a dose dependent and saturable manner, with IC50 of 4 microM and maximal inhibition (about 70%) at 6 microM. Scanning electron microscope (SEM) analysis showed that addition of RG12986 to whole blood significantly inhibited platelet aggregation on ECM. The extent of inhibition observed with RG12986 at a final concentration of 4 microM was similar to that obtained with the cell adhesion peptide RGDS at the concentration of 0.1 mM. The ability of the RG12986 fragment to inhibit platelet aggregation on ECM is in agreement with the concept that blockade of vWF-GPIb interaction may inhibit further events leading to activation of the glycoprotein IIb/IIIa (GPIIb/IIIa) complex and subsequent thrombus formation.

Amino Acid Sequence↗
PubMed1993

Effect of basic fibroblast growth factor on the growth and differentiation of adult stromal bone marrow cells: enhanced development of mineralized bone-like tissue in culture.

Rat stromal bone marrow cells (SBMC) were shown to produce mineralized bone-like tissue in culture in the presence of dexamethasone, ascorbic acid, and beta-glycerophosphate. The addition of 3 ng/ml of basic fibroblast growth factor (bFGF) resulted in a significant increase in formation of mineralized tissue. The present study was aimed at assessing the effect of bFGF on the proliferation and differentiation of SBMC and on the sequential development of mineralized bone-like tissue in culture. Transmission electron microscopy of bFGF-treated cultures demonstrated the development of a multilayered structure resembling mineralized bone tissue consisting of cell layers embedded within a heavy extracellular matrix. The matrix was rich in bundles of collagen fibers associated with extensive mineral deposits consisting of hydroxyapatite as determined by infrared spectrophotometry. The addition of 3 ng/ml of bFGF resulted in significant enhancement of [3H]thymidine and [3H]proline incorporation and protein accumulation by 12-, 2.5-, and 2.5-fold, respectively. bFGF treatment increased cAMP responsiveness, alkaline phosphatase activity, osteocalcin level, 45Ca2+ deposition, and mineralized-like tissue formation and induced the earlier expression of these markers in the treated culture. A biphasic sequence of events was observed during the development of mineralized bone-like tissue in bFGF-treated and control cultures. The first phase is characterized by cell proliferation and matrix accumulation and is reflected by a progressive increase in [3H]thymidine and [3H]proline incorporation until day 11. The second phase, which follows, is characterized by a sharp decline in cell proliferation and matrix accumulation and a concomitant expression of osteoblast differentiation as reflected by the progressive increase in alkaline phosphatase activity, mineral deposition, and osteocalcin expression. Treatment of cultures with bFGF accentuated this biphasic sequence of events. These results indicate that bFGF has the capacity to stimulate both the growth and the biochemical functions of SBMC obtained from a young adult animal.

Alkaline Phosphatase↗
PubMed1993

Platelet protection by low-dose aprotinin in cardiopulmonary bypass: electron microscopic study.

To evaluate the effect of low-dose aprotinin during cardiopulmonary bypass on platelet function and clinical hemostasis, 30 patients undergoing various cardiopulmonary bypass procedures employing bubble oxygenators were randomized to receive either low-dose aprotinin (2 x 10(6) KIU in the cardiopulmonary bypass priming solution, 15 patients [group A]) or placebo (15 patients [group B]). Blood samples were collected before and after cardiopulmonary bypass to assess platelet count and aggregation on extracellular matrix, which was studied by a scanning electron microscope. On a scale of 1 to 4 preoperative mean platelet aggregation grades were similar in both groups (3.8 +/- 0.5 and 3.5 +/- 0.5 for groups A and B, respectively). Postoperatively, platelet aggregation on extracellular matrix decreased slightly in group A (2.8 +/- 1.3; p < 0.01) and significantly in group B (1.3 +/- 0.5; p < 0.001). Eleven of the 15 patients in group A remained in aggregation grade 3 or 4 compared with none of the group B patients. Platelet count was similar in both groups preoperatively and postoperatively. Total 24-hour postoperative bleeding and blood requirement were lower in the aprotinin group (487 +/- 121 mL and 2.3 +/- 1.0 units) than in the placebo group (752 +/- 404 mL and 6.8 +/- 5.1 units; p < 0.01). These results show that the use of low-dose aprotinin during cardiopulmonary bypass provides improved postoperative hemostasis, which might be related to the protection of the platelet aggregating capacity.

Aged↗
PubMed1993

Sphingomyelin biosynthesis and efflux correlates with cholesterol metabolism and is higher in vascular endothelial cells than in smooth muscle cells.

We compared the metabolism of cellular phospholipids in bovine aortic endothelial and smooth muscle cells in culture. [3H]Choline was incorporated in both cell types into phosphatidylcholine (86-90%) and sphingomyelin (10-14%). Endothelial cells demonstrated preferential efflux of sphingomyelin which represented 22.5% of the radiolabelled phospholipids in the incubation medium while in smooth muscle cells it represented 10%, so that after 7 days, the sphingomyelin in the medium represented 40% and 16% of total synthesized sphingomyelin in endothelial and smooth muscle cells, respectively. Incorporation of [3H]choline by endothelial and smooth muscle cells was reduced in the presence of serum, but not in the presence of lipoprotein deficient serum, indicating that cells can acquire phosphatidylcholine and sphingomyelin from lipoproteins. Lipoproteins were shown also to support the efflux of cellular radiolabelled phospholipids from both cell types, but at a higher degree from endothelial cells than from smooth muscle cells. Exposure of these cultures to cholesterol rich serum increased the synthesis of phosphatidylcholine, and to a higher extent of sphingomyelin, with concomitant decrease in the efflux of these two phospholipids. These results demonstrate the role of cholesterol in the regulation of phosphatidylcholine and sphingomyelin biosynthesis and efflux in vascular cells. Furthermore, the higher efflux of sphingomyelin in endothelial cells than in smooth muscle cells may support the extensive efflux of cholesterol observed in endothelial cells and indicate biochemical differences in lipid metabolism between vascular endothelial and smooth muscle cells.

Animals↗
PubMed1993

Role of apolipoproteins A-I, A-II and C-I in cholesterol efflux from endothelial and smooth muscle cells.

The role of purified apolipoproteins A-I, A-II and C-I in the process of cholesterol efflux from cultured vascular endothelial and smooth muscle cells was studied. [3H]Cholesterol pre-labelled cultures were exposed to serum-free medium supplemented with free apolipoproteins or with apolipoproteins and phosphatidylcholine liposomes and the cholesterol efflux from the cells was determined. Free apolipoproteins A-I and A-II supported cholesterol efflux from vascular endothelial and smooth muscle cells to a higher extent than apolipoprotein C-I. The ability of free apolipoproteins A-I and A-II to support cholesterol efflux was in correlation with their specific binding to the cultures, while no specific binding of apolipoprotein C-I was detected. The association of apolipoprotein A-I with phosphatidylcholine liposomes resulted in a more than two-fold increase in cholesterol efflux compared to free apolipoprotein A-I, while association of apolipoproteins A-II and C-I with phosphatidylcholine liposomes resulted in a very limited increase in cholesterol efflux above that achieved by the free apolipoproteins. These results suggest that apolipoprotein A-I is involved in cholesterol efflux performed by high density lipoprotein. Furthermore, free apolipoproteins A-I and A-II, but not apolipoprotein C-I may take an active part in cholesterol efflux from endothelial and smooth muscle cells.

Animals↗