Biomedical subjects

S Dejager

Publications and source records attributed to S Dejager.

At least 19 recordsLinked to original sources

PubMed2006

Prevalence of low HDL-cholesterol in patients with cardiovascular risk factors: The ECHOS (Etude du Cholesterol HDL en Observationnel) French Survey.

A low concentration of high-density lipoprotein-cholesterol (HDL-C) is an independent risk factor for cardiovascular heart disease (CHD), but little is known about the distribution of HDL-C in France. This study evaluated the prevalence of low HDL-C among a large French population (5232 patients) with other cardiovascular risk factors. Depending on the guidelines used, the prevalence of low HDL-C varied from 8.7% (cutoff value of 35 mg/dl) to 26.9% (National Cholesterol Education Program metabolic syndrome cutoff values). The prevalence of low HDL-C gradually increased with the number of associated risk factors. We identified three independent risk predictors for low HDL-C: hypertriglyceridaemia (HTG), abdominal obesity and gender. Overall, the frequency of HDL-C assessment was very high (>85%) and it was highest in patients with hypercholesterolaemia or a history of CHD. Risk factors more frequently associated with low HDL-C (i.e. HTG, abdominal obesity and type 2 diabetes) were not associated with a more frequent assessment of HDL-C. Our findings indicate that in France, the prevalence of low HDL-C remains relatively high, particularly for patients with obesity and HTG.

Body Mass Index↗

PubMed2004

Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study.

There are few effective, safe modalities for the management of Graves' ophthalmopathy (GO), a cell-mediated immune comorbidity of thyroid disease. Somatostatin analogs inhibit lymphocyte proliferation and activation, and accumulate in the orbital tissue of patients with GO. A double-blind, placebo-controlled study of a long-acting somatostatin analog [16 wk of long-acting release formulation of octreotide (octreotide-LAR)] was conducted in 51 patients with mild active GO with the aim of preventing deterioration and precluding the need for more aggressive therapeutic modalities, such as glucocorticoids or radiotherapy. No treatment effect was observed for the primary end point (a composite parameter defining the outcome as either success or failure on the basis of changes in class/grade of the severity index and Clinical Activity Scale of GO). The Clinical Activity Scale score was reduced for patients treated with octreotide-LAR, but without any significant difference with respect to patients receiving placebo. However, octreotide-LAR significantly reduced proptosis (as measured by exophthalmometry). This was associated with nonsignificant differences in favor of octreotide-LAR in a series of proptosis-related parameters: class III grade, opening of the upper eyelid, the difference in ocular pressure between primary position and upgaze, and extraocular muscle involvement. By magnetic resonance imaging evaluation the extraocular muscle volumes appeared reduced, but nonsignificantly. No significant correlation between the initial uptake of the somatostatin analog indium-labeled and the response to treatment was observed. One patient in the octreotide-LAR group developed gallstones. In this study, octreotide-LAR did not seem suitable to mitigate activity in mild GO. Surprisingly, it significantly reduced proptosis, one of the most debilitating symptoms of GO. Additional studies are warranted to define the benefit to risk ratio of the somatostatin analogs in this indication.

Delayed-Action Preparations↗

PubMed2004

[The PACIFIQUE registry in post PCI patients: study protocol].

This paper presents the protocol of the PACIFIQUE survey, carried out in the most important French interventional cardiology centres (>600 procedures/year) during a 2-week period in January 2004, in order to determine actual practices in terms of medical management at hospital discharge and 6-month follow-up in patients treated with coronary angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed2002

A comprehensive endocrine description of Kennedy's disease revealing androgen insensitivity linked to CAG repeat length.

Our study aims to provide a comprehensive view of the endocrine features in Kennedy's disease (KD). Twenty-two men with KD underwent detailed endocrine investigations. Clinical signs of partial androgen resistance were present in more than 80% of the patients, with gynecomastia being the most prominent. Gynecomastia was postpubertal but appeared before muscular weakness in most cases. Thirteen patients had alteration of testicular exocrine function. Hormonal profile of partial androgen resistance was present in 86% of the patients, with an elevated testosterone level in 68%. Androgen insensitivity seems to appear later in life in KD, similar to the development of neurological signs. Although we confirm the previously reported correlation between the CAG repeat length and the early onset of the neurological disease, we describe a significant correlation between repeat length and the age of onset of gynecomastia as well as biological indexes of androgen insensitivity. This is supported by numerous in vitro data correlating variations in the CAG tract with androgen receptor activity; the longer the CAG repeats, the weaker the receptor transactivation. Ours is the first study to show such a clear and prominent pattern of androgen insensitivity in KD. In clinical practice, KD patients are often misdiagnosed as having amyotrophic lateral sclerosis. Careful examination of the endocrine component could avoid such a deleterious misdiagnosis.

Adult↗

PubMed2001

Smaller LDL particle size in women with polycystic ovary syndrome compared to controls.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. The contribution of lipid abnormalities to this higher risk, in particular atherogenic modifications of low density lipoprotein (LDL) such as a shift towards smaller LDL, has not been properly explored. We aimed to examine LDL size variation in relation to androgens and other risk factors in women with PCOS. DESIGN: Comparison of clinical and biochemical measurements in women with PCOS and women with normal ovarian function, of similar age and body mass index (BMI). PATIENTS: Thirty-one women with PCOS and 27 controls were studied. Patients were recruited from the outpatient endocrine clinic. MEASUREMENTS: Fasting total cholesterol, triglycerides (TG), high density lipoprotein (HDL), LDL, glucose, insulin, gonadotrophins, androgens, oestradiol, 17 OH progesterone and SHBG were measured. LDL particle diameter was calculated based on distance travelled in polyacrylamide native gels. Recumbent blood pressure was measured automatically. RESULTS: LDL particle size appeared to be significantly smaller in hyperandrogenic PCOS as compared to regularly cycling women (P = 0006), independent of variations in lipid levels. SHBG was the only independent predictor of LDL size in this population, with a strong correlation, which persisted after adjustment for all confounding variables. CONCLUSIONS: Our results suggest that androgen excess and mild insulin-resistance (both responsible for lower SHBG) may have an early modifying effect on low density lipoprotein size in polycystic ovary syndrome women. The denser pattern observed in polycystic ovary syndrome women could by itself constitute a higher cardiovascular risk, even in the absence of overt dyslipidaemia, and contribute to the excess risk of cardiovascular disease reported in this syndrome.

Adult↗

PubMed2000

Effect of combined fluvastatin-fenofibrate therapy compared with fenofibrate monotherapy in severe primary hypercholesterolemia. French Fluvastatin Study Group.

This double-blind study was designed to assess the efficacy and safety of fluvastatin-fenofibrate combination therapy compared with fenofibrate monotherapy in severe primary hypercholesterolemia (low-density lipoprotein [LDL] cholesterol > or =190 mg/dl [4.9 mmol/L], triglycerides < or =350mg/dl [3.9 mmol/l]). After a 10-week placebo and dietary baseline period, 102 patients were randomized to receive micronized fenofibrate 200 mg, fluvastatin 20 mg plus micronized fenofibrate 200 mg, or fluvastatin 40 mg plus micronized fenofibrate 200 mg. At week 16, fenofibrate 200 mg alone lowered LDL cholesterol from baseline by 21% compared with 32% for fluvastatin 20 mg plus fenofibrate 200 mg and 41% for fluvastatin 40 mg plus fenofibrate 200 mg (p <0.001). Triglycerides decreased by 29% with fenofibrate 200 mg alone, 39% with fluvastatin 20 mg plus fenofibrate 200 mg, and 40% with fluvastatin 40 mg plus fenofibrate 200 mg (p <0.05). Safety was assessed by recording adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for the 3 treatment groups. One patient withdrew due to an increase in transaminase levels. No significant increase in creatine phosphokinase levels was observed with combination therapy. In conclusion, the addition of fluvastatin to micronized fenofibrate results in substantial improvement in atherogenic plasma lipids and is well tolerated.

Aged↗

PubMed2000

Time course of GH and IGF-1 levels following withdrawal of long-acting octreotide in acromegaly.

AIM: Several studies have demonstrated the efficacy of octreotide LAR administered intramuscularly at 4-week intervals in the treatment of acromegaly. In contrast, few data are available on the time course of GH and IGF-1 plasma levels following octreotide LAR withdrawal. This prompted us to study these parameters for up to 20 weeks following drug withdrawal in a group of 18 acromegalic patients treated for one year. DESIGN AND PATIENTS: We studied 18 patients treated with octreotide LAR 10 mg (n = 2), 20 mg (n = 15) and 30 mg (n = 1) every 4 weeks for one year. GH (mean level during a 4-hour daily profile) and IGF-1 concentrations were measured at the end of treatment, just before the last injection (baseline) and then 15 +/- 2 weeks (first control) after the last injection. In patients with GH levels below 2.5 micrograms/L and/or normal IGF-1 at the first control, a second control was performed four to eight weeks later. RESULTS: After one year of treatment with octreotide LAR, the mean plasma GH concentration was 1.91 +/- 1.25 micrograms/L (mean +/- SE) and the mean IGF-1 concentration was 440 +/- 251 micrograms/L. Among the 18 patients, 13 had mean plasma GH concentrations below 2.5 micrograms/L and seven could be considered as well-controlled (normal IGF1 and mean GH levels below 2.5 micrograms/L). After treatment withdrawal, the plasma GH concentration remained below 2.5 micrograms/L at the first and the second controls in 2 of the 13 (15%) patients with suppressed GH levels on baseline. Among the seven well-controlled patients on baseline (GH levels below 2.5 micrograms/L and normal IGF-1), one (15%) remained well-controlled, one (15%) kept GH levels below 2.5 micrograms/L but increased IGF-1 levels, and one (15%) kept normal IGF-1 levels but increased mean GH levels at the first control. This hormonal status remained unchanged at the second control in these 3 patients. CONCLUSIONS: These results show long-lasting suppression of GH secretion after treatment withdrawal in some acromegalic patients treated for 12 months with octreotide LAR. The duration of GH suppression after treatment withdrawal is variable. Mean GH levels remained below 2.5 micrograms/L in 15% of our patients for up to 21 weeks following withdrawal of octreotide LAR. In practice, it may be preferable to wait several months after long-acting somatostatin analog withdrawal before reassessing hormone status. Owing this long-lasting effect, a dose reduction to 10 mg and/or a longer interval between injections could be considered for very good responders, as this would lead to considerable cost savings without affecting GH or IGF-1 control.

Acromegaly↗

PubMed1999

Relationship between triglycerides and factor VIIc and plasminogen activator inhibitor type-1: lack of threshold value.

Increased factor VIIc (FVIIc) and plasminogen activator inhibitor type 1 (PAI-1) levels may lead to a thrombotic state and subsequently to a higher risk of myocardial infarction. The relationships between triglycerides and plasma levels of both PAI-1 and FVIIc were established in previous studies. However, there is no data assessing whether there is a threshold value of triglycerides above which FVIIc and PAI-1 levels increase or whether the relationship is continuous. Therefore, we measured triglycerides, FVIIc, and PAI-1 levels in a large group of 1254 asymptomatic patients with hyperlipoproteinemia. Our results showed that both FVIIc and PAI-1 levels increase linearly in parallel to triglyceride levels (p=0.0001). In the multiple regression analysis, the relationship between log triglycerides and FVIIc was significantly independent of total cholesterol, body mass index, fasting glycemia, gender, and age; the relationship between log triglycerides and PAI-1 was significantly independent of body mass index, fasting glycemia, gender, and age. Interestingly, we found that the correlation coefficients between triglycerides and the haemostatic parameters measured were almost identical in different subgroups of subjects: males, females, nonobese, and normoglycemic, as well as nonalcoholic. We conclude that the relationships between triglyceride levels and FVIIc, as well as PAI-1, are continuous without threshold value of triglycerides.

Adsorption↗

PubMed1998

Sheehan's syndrome: differential diagnosis in the acute phase.

Many studies have been done in the later course of Sheehan's syndrome, but very few have documented the acute phase with clinical, endocrine and imaging data. We present the case of a young woman complaining of severe headache after delivery, who developed hypopituitarism. Magnetic resonance imaging (MRI) disclosed the presence of an enlarged non haemorrhagic pituitary gland. Follow-up MRI showed a spontaneous and rapid shrinkage of the pituitary, within 20 days, which appeared as an empty sella 3 months later. Sheehan's syndrome may initially closely mimic hypophysitis, or the necrosis of an adenoma. We discuss the differential diagnoses, important for the best therapeutic management.

Acute Disease↗

PubMed1997

[Lipid risk factors of atherosclerosis: who, when, how to treat?].

Hyperlipidemia, particularly hypercholesterolemia, is a well established risk factor for cardiovascular disease, specially coronary heart disease. Lipid-lowering therapies are associated with a reduction in cardiovascular morbidity and mortality in secondary as well as primary prevention. A precise lipid pattern is necessary before any treatment. The target level depends on the clinical data and associated cardiovascular risk factors. Diet is the first step approach and should always be continued. Cholestyramine and statins are the treatments of choice in case of hypercholesterolemia (type IIa). In case of isolated or associated hypertriglyceridemia (types IV and IIb) fibrates are the most efficient. No treatment is really efficient on Lp(a) level. A good observance is required for a lifelong treatment.

Child↗

PubMed1996

[Hyperlipidemia in pregnancy].

Hyperlipidemia is one of the most striking modification of biological parameters occurring during normal pregnancy. Hypertriglyceridemia is the most prominent feature, with a less dramatic increase of total cholesterol levels. Besides these quantitative changes, most lipoproteins undergo qualitative modification throughout pregnancy such as triglyceride enrichment of the particles. Kinetics and magnitude of plasma lipids changes have been well recognized, but the mechanisms, metabolic fate and impact on the pathogenesis of cardiovascular disease are not totally unravelled. The primary modulators are estrogens, insulin and lipoprotein lipase. Hyperlipidemia is a result of the metabolic adaptation of the maternal organism to pregnancy allowing to save glucose and energy for the fetus, reversible within a few weeks in postpartum. However some have suggested a trend toward an increased risk for coronary disease after multiple pregnancies. In case of preexisting hyperlipidemia, whether familial or not-primary or secondary, pregnancy presents an additional challenge. Except from exceptional complications, dietary counselling will be the only treatment, under a close follow-up.

Female↗

PubMed1995

[Atherogenicity of low-density lipoproteins (LDL). A problem of quantity or quality?].

The relationship between elevated plasmatic LDL and increased risk of coronary artery disease is definitively established. However the qualitative aspect of the particles also appear to play a significant role: a structural heterogeneity within the LDL particles themselves has been recognized for a number of years. Multiple subclasses have been characterized in several populations of normal and hyperlipidaemic subjects. Some of these subclasses are linked with an atherogenic potential, this is the case for the smaller and the more dense of the particles, defined as the phenotype B. Epidemiological studies have consistently shown an association of this phenotype with an increased risk of coronary artery disease, and various reports have linked it with clinical and angiographic indices of the disease. However, these studies do not allow for causality, and after adjustment for the plasma TG level LDL subclasses distribution is not an independent predictor of coronaropathy anymore. The underlying mechanisms leading to the association are not yet established, but it is possible that small dense LDL are per se atherogenic. Considerable evidence is now available to support some of the hypothesis: denser LDL have a lower affinity for the LDL BE receptor, are more succeptible to oxidative damage, and may have modified interaction with various components of the arterial wall. Moreover several authors have shown that a number of lipid lowering drugs, like fibrates, could normalize to a significant extent the plasma profile of LDL as a result of preferential reduction in the elevated levels of the denser more atherogenic subspecies.

Arteriosclerosis↗

PubMed1994

[Lipoprotein lipase: a key enzyme of lipid metabolism].

Lipoprotein lipase (LPL), a 55 kDa secretory glycoprotein produced in numerous tissues, is a hydrolytic enzyme, rate-limiting for the removal of lipoprotein TG from the circulation. It is activated by apoprotein CII present on TG-rich lipoproteins. It is involved in lipid transfer between lipoproteins, and plays an important role in the formation of HDL. The fate of LPL-derived lypolysis products differs between tissues: for instance, in adipose tissue, LPL-mediated delivery of free fatty acids is rate-limiting for TG storage, whereas in muscle it provides an alternate source of lipid fuel. LPL is regulated by hormones like insulin and nutrients; its activity depends on the metabolic state of the tissue. It has distinct roles in many normal tissues, such as adipocytes or muscles, as well as an important role in atherogenic dyslipidemia and in metabolic diseases including obesity and hypertriglyceridemia.

Humans↗

PubMed1993

Ciprofibrate therapy normalises the atherogenic low-density lipoprotein subspecies profile in combined hyperlipidemia.

The effect of ciprofibrate treatment on the atherogenic profile of low-density lipoprotein (LDL) subspecies in combined hyperlipidemia (CHL) has been investigated in six patients displaying elevated plasma triglyceride and cholesterol levels (> 200 and > 250 mg/dl, respectively). The E2E2 phenotype was excluded; four patients possessed familial antecedents of premature coronary heart disease (CHD). Analysis of five LDL subclasses separated by isopycnic density gradient ultracentrifugation showed a predominance of dense LDL subspecies (LDL-4 and LDL-5, d 1.039-1.063 g/ml; 51% of total LDL mass) in the asymmetric LDL density profile characteristic of CHL patients at baseline. Ciprofibrate treatment (100 mg/day for 1 month) effected marked reductions in both total plasma LDL and apo B-100 levels (approximately 19% and approximately 23%, respectively). Equally, the plasma profile of LDL subspecies was normalised to a significant degree as a result of preferential reduction in the elevated levels of both dense subspecies (LDL-4 and LDL-5; -43% and -54%, respectively; P < 0.03 and P < 0.006 [corrected], respectively). The circulating concentrations of light LDL (LDL-1, d 1.019-1.023 g/ml) were also diminished significantly by ciprofibrate (-30%; P < 0.006 [corrected]). Furthermore, ciprofibrate not only effected reductions in the elevated triglyceride content of the hydrophobic core of all LDL subspecies but also normalised their common deficiency in free cholesterol. In addition, the abnormally small particle diameters of LDL-4 and -5 were increased to normal. Plasma levels of both apo B-100 and triglycerides were significantly and positively correlated with those of LDL-4 and LDL-5, suggesting not only that the degree of triglyceride elevation is intimately linked to the extent of shift in LDL subclass profile towards denser subspecies, but also that triglyceride reduction upon treatment strongly influences LDL-4 and LDL-5. In conclusion, our findings indicate that ciprofibrate treatment in combined hyperlipidemia results in marked reduction in plasma triglyceride levels (-33%), and that such reduction is intimately linked to normalisation of both the qualitative and quantitative features of the atherogenic LDL subspecies profile typical of this disorder.

Adult↗

PubMed1993

Oxidized low density lipoproteins bind to the scavenger receptor expressed by rabbit smooth muscle cells and macrophages.

We have previously demonstrated that the acetylated low density lipoprotein (LDL), or scavenger, receptor expressed by rabbit smooth muscle cells (SMCs) is regulated. Phorbol ester treatment of the cells increased the number of scavenger receptors expressed and the metabolism of acetoacetylated (AcAc) LDL. The current studies examined the interaction of oxidized (Ox) LDL with the rabbit scavenger receptor. The internalization and degradation of both Ox-LDL and AcAc-LDL were increased to a similar extent by phorbol ester treatment of the SMCs. In cross-competition experiments, both Ox-LDL and AcAc-LDL competed equally for the degradation of 125I-Ox-LDL, suggesting that there is no independent receptor for Ox-LDL on these cells. In contrast, only AcAc-LDL competed totally for the degradation of 125I-AcAc-LDL. Similar results were obtained in cross-competition experiments with rabbit macrophages. To determine whether these data were consistent with the binding of both ligands to a single receptor, competition studies were conducted in Chinese hamster ovary fibroblasts transfected with the bovine scavenger receptor. After transfection, the metabolism of both AcAc-LDL and Ox-LDL was increased, in agreement with the previous data from other investigators, and cross-competition studies yielded essentially identical results to those obtained in the SMCs and macrophages. Northern blot analysis with an antisense rabbit scavenger receptor probe detected the same mRNA species in total RNA from rabbit macrophages and SMCs and showed that scavenger receptor mRNA increased dramatically after phorbol ester treatment of SMCs. The probe also detected bovine scavenger receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Dominant negative mutations of the scavenger receptor. Native receptor inactivation by expression of truncated variants.

The bovine scavenger receptor was truncated at amino acid 266 or 310 to delete either all or part, respectively, of the collagen-like domain. The truncated receptors were inactive in the binding and internalization of acetyl (Ac) low density lipoprotein (LDL). Coexpression of truncated receptor with the native receptor dramatically reduced the percentage of cells internalizing fluorescently labeled Ac LDL, compared with cells expressing the native receptor alone. The mutant truncated at amino acid 266 was most effective in receptor inactivation, resulting in a 42% or 80% decrease in the percentage of cells expressing active receptor when transfected in a 1:1 or 1:2 molar ratio (native:mutant), respectively, with native receptor. Degradation of 125I-Ac LDL was reduced up to 90% when the native and truncated mutant receptors were coexpressed. Scavenger receptor inhibition was specific because the activity of the LDL receptor was not altered. Transient transfection of the mouse macrophage cell line P388D1 with truncated scavenger receptor resulted in a 65% decrease in the uptake and degradation of Ac LDL but did not decrease the degradation of beta-migrating very low density lipoprotein, which is LDL receptor-mediated. These results demonstrate that expression of truncated bovine scavenger receptor inactivates both the native bovine and murine scavenger receptors, producing a dominant negative phenotype in vitro.

Animals↗

PubMed1993

Dense low density lipoprotein subspecies with diminished oxidative resistance predominate in combined hyperlipidemia.

Patients presenting combined hyperlipidemia (CHL) display an elevated risk of coronary heart disease. The atherogenic lipoprotein particles implicated in this disorder remain ill defined. We determined the qualitative and quantitative characteristics of the density distribution of low density lipoprotein (LDL) particle subspecies in nine subjects defined phenotypically as presenting CHL, and under strict dietary control. Seven CHL patients possessed familial antecedents of premature coronary heart disease; none were E2E2 homozygotes. Five LDL subspecies were isolated by density gradient ultracentrifugation in the density range 1.019-1.063 g/ml. In all patients, the LDL profile was skewed towards the dense subspecies (LDL-4, d 1.039-1.050 g/ml and LDL-5, d 1.050-1.063 g/ml), representing 47% of total LDL mass; by contrast, these subspecies accounted for only 30% of LDL mass in five normolipidemic subjects (P < 0.01). In addition, plasma LDL mass concentrations were some twofold higher in CHL patients as compared to normolipidemic subjects. The % mass of LDL-4 was positively correlated with plasma triglyceride and apoB levels. LDL-2 and LDL-3 in CHL patients were triglyceride-enriched (11.9 and 7.2%, respectively) as compared to the corresponding subspecies in normolipidemic subjects (6.6 and 3.7%, respectively; P < 0.05 in each case). LDL particle size decreased with increase in density in both groups; however, significant differences were found between corresponding LDL subspecies (LDL-1, -3, -4, and -5) in CHL patients and normolipidemic subjects, a finding suggestive of dissimilar molecular organization, despite correspondence in hydrated density. The copper-induced oxidative modification of LDL subspecies was assessed by determination of conjugated diene formation. In both groups, LDL-5 was distinct in exhibiting a marked diminution in oxidative resistance as indicated by a significant reduction (P < 0.01) in mean lag time. The oxidative susceptibility of LDL subspecies in both groups was independent of vitamin E content when expressed as the ratio vitamin E/LDL mass, although dense LDL in CHL patients tended to be deficient in this antioxidant. The diminished oxidative resistance of dense LDL subspecies could not be accounted for by enrichment in polyunsaturated fatty acids in either group. These studies suggest that in consequence of their elevated circulating concentration and diminished oxidative resistance, dense LDL subspecies represent putative atherogenic subspecies in combined hyperlipidemia.

Adult↗

PubMed1992

Further characterization of the acetyl LDL (scavenger) receptor expressed by rabbit smooth muscle cells and fibroblasts.

We have previously demonstrated that the acetyl low density lipoprotein (LDL), or scavenger, receptor is expressed by rabbit smooth muscle cells (SMCs) and fibroblasts. Moreover, receptor activity in rabbit fibroblasts was regulated over a wide range by preincubating the cells with secretion products from human platelets or with phorbol esters. The current studies were undertaken to examine the regulation of receptor expression in rabbit SMCs, to characterize further the receptor expressed by rabbit SMCs and fibroblasts, and to determine whether incubating these cells with chemically modified lipoproteins would lead to foam cell formation. Receptor activity was increased fivefold in rabbit SMCs by preincubation with platelet secretion products and nine- to 20-fold by preincubation with phorbol esters or mezerein, a non-phorbol activator of protein kinase C. The phorbol ester-induced increase in receptor activity was due to an increased mass of scavenger receptor as determined by both ligand blots and immunoblots of membrane proteins from these cells. The immunoblotting studies suggest that the SMC scavenger receptor activity is due to type I or type II scavenger receptors. The scavenger receptor expressed by phorbol ester-treated rabbit SMCs and fibroblasts bound chemically modified LDL with an order-of-magnitude higher affinity (Kd 5.1 x 10(-10) M) than did the scavenger receptor expressed by mouse peritoneal macrophages (Kd 4.1 x 10(-9) M), whereas rabbit macrophages bound chemically modified LDL with intermediate affinity (Kd 1.0 x 10(-9) M). Both the phorbol ester-stimulated rabbit fibroblasts and SMCs expressed 10-30% as many receptors per cell as did mouse peritoneal macrophages. Consistent with the difference in the number of receptors, uptake of the chemically modified LDL at 37 degrees C by SMCs led to approximately 25% as much lysosomal degradation and stimulation of cholesterol esterification as in mouse peritoneal macrophages. Incubation of phorbol ester-treated rabbit fibroblasts or SMCs with chemically modified LDL (50 micrograms/ml) for 24 or 48 hours, respectively, resulted in a threefold increase in total cholesterol and a 15-fold increase in cholesteryl ester within the cells. These studies suggest that the scavenger receptor-mediated uptake of modified lipoproteins may contribute to the formation of SMC foam cells in atherosclerotic lesions.

Animals↗