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Biomedical subjects

A Sniderman

Publications and source records attributed to A Sniderman.

At least 19 recordsLinked to original sources
PubMed1999

Mechanisms involved in the regulation of free fatty acid release from isolated human fat cells by acylation-stimulating protein and insulin.

The effects of acylation-stimulating protein (ASP) and insulin on free fatty acid (FFA) release from isolated human fat cells and the signal transduction pathways to induce these effects were studied. ASP and insulin inhibited basal and norepinephrine-induced FFA release by stimulating fractional FFA re-esterification (both to the same extent) and by inhibiting FFA produced during lipolysis (ASP to a lesser extent than insulin). Protein kinase C inhibition influenced none of the effects of ASP or insulin. Phosphatidylinositol 3-kinase inhibition counteracted the effects of insulin but not of ASP. Phosphodiesterase 3 (PDE3) activity was stimulated by ASP and insulin, whereas PDE4 activity was slightly increased by ASP only. Selective PDE3 inhibition reversed the effects of both ASP and insulin on fractional FFA re-esterification and lipolysis. Selective PDE4 inhibition slightly counteracted the ASP but not the effect of insulin on fractional FFA re-esterification and did not prevent the action of ASP or insulin on lipolysis. Thus, ASP and insulin play a major role in regulating FFA release from fat cells as follows: insulin by stimulating fractional FFA re-esterification and inhibiting lipolysis and ASP mainly by stimulating fractional FFA re-esterification. For both ASP and insulin these effects on FFA release are mediated by PDE3, and for ASP PDE4 might also be involved. The signaling pathway preceding PDE is not known for ASP but involves phosphatidylinositol 3-kinase for insulin.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

Plasma acylation-stimulating protein in coronary artery disease.

To date, plasma levels of acylation-stimulating protein (ASP) have been determined only in normal and obese individuals. Accordingly. ASP was measured in fasting samples obtained from 59 age-matched controls and 208 patients with documented coronary artery disease (CAD). Overall, plasma ASP was significantly higher in the CAD subjects compared to the control subjects (55.3 +/- 1.8 nmol/L CAD versus 32.0 +/- 2.6 nmol/L control, P < .0005). In the control group, the distribution of plasma ASP values was unimodal whereas in the coronary group it was significantly skewed to the right. The coronary group was subdivided into those with pronounced elevation of apoB (a marked type II phenotype, n = 13), those with hypertriglyceridemia with a normal apoB (n = 17), and the remaining CAD subjects (n = 178). In the first two groups, ASP did not differ significantly from control subjects (43 +/- 2.8 nmol/L and 49 +/- 4.4 nmol/L respectively). By contrast, in the remaining CAD subjects, both the mean ASP level (56.8 +/- 2.0 nmol/L, P < .001 by ANOVA) and the proportion of patients with a markedly elevated ASP (25.3% were > 95th percentile, P < .005 versus control by X2) were significantly increased. When this third group was divided into tertiles by plasma apoB and triglyceride there was a direct relationship between plasma ASP and these two parameters. Linear regression analysis demonstrated an association between plasma ASP and plasma triglyceride (P < .05), VLDL cholesterol (P < .025), and VLDL apoB (P < .05). Finally, when all of the CAD subjects were divided by apoE phenotype, there appeared to be a relationship between plasma ASP and apoE phenotype such that ASP was higher in E2 subjects, intermediate in E3 subjects, and lower in E4 subjects. The present data document plasma ASP levels in a number of dyslipoproteinemic states and suggest a relation between the adipsin-ASP pathway and other metabolic determinants of lipoprotein metabolism.

Acylation↗
PubMed1996

Cardiovascular disease in peritoneal dialysis.

Cardiovascular morbidity and mortality remain high in ESRD patients. Lipid abnormalities in CAPD may be more important than in hemodialysis. Vessel calcification may have a role in atherosclerotic heart disease, but this is only an inference from several clinical observations, and it remains to be defined more clearly as a risk factor. Left ventricular hypertrophy is frequent in this patient population, and is associated with specific clinical patterns and an increased risk of death. Erythropoietin treatment of anemia and tight blood pressure controls have proved to help in reversing severe left ventricular hypertrophy. Finally, we describe a syndrome of the hypertrophic, high cardiac output hemodialysis heart, which is characterized by a high cardiac output in hemodialysis patients. It is associated with left ventricular hypertrophy and eventually right ventricular hypertrophy with tricuspid insufficiency. This may require fistula revision and even a switch peritoneal dialysis.

Cardiovascular Diseases↗
PubMed1996

[Adipsin system--acylation-stimulation protein (ASP) and hyperapo-B].

Acylation Stimulating Protein (ASP) is a small basic protein which was isolated from the human plasma and which has been shown to be the most potent stimulant yet discovered of triglyceride synthesis. The initial observation were made in vitro, but there is now in vivo evidence that the adipsina-ASP system has an important regulatory role in triglyceride clearance from plasma. Studies in normals have shown that the higher the fasting and the peak ASP plasma levels are after an oral fat load, the faster the triglyceride clearance from plasma. Moreover, decreased function of the adipsina-ASP system appears to lead to increased delivery of free fatty acids and triglyceride-rich chylomicron remnants to the liver with a consequent increase in the rate of secretion of B100 lipoprotein particles. That is to say, defective function of this system is one of the causes of hyperapoB which in turn is one of the commonest dyslipoproteinemias associated with premature coronary artery disease.

Apolipoproteins B↗
PubMed1995

The acylation stimulating protein-adipsin system.

Considerable evidence indicates that obesity, and in particular abdominal obesity, is a risk factor for both heart disease and non-insulin dependent diabetes mellitus. In spite of this, little is known of the regulation of triacylglycerol synthesis in adipose tissue other than by insulin. Acylation stimulating protein (ASP), a human plasma protein, stimulates triacylglycerol synthesis in adipose tissue and is also produced by human adipocytes. ASP may play a physiological role in the regulation of efficiency of adipose tissue fat storage and affect clearance of triglycerides from plasma.

3T3 Cells↗
PubMed1991

Effect of moderate hypertriglyceridemia on the relation of plasma total and LDL apo B levels.

The risk of premature coronary artery disease is related to an important degree to the number of particles of low density lipoproteins (LDL) in plasma, an estimate given by measurement of LDL apo B. In clinical practise, though it is total, not LDL apo B, which is measured. The purpose of the present study therefore was to compare plasma total and LDL apo B in the presence and absence of moderate hypertriglyceridemia. The results demonstrate that within the range of plasma triglyceride levels examined, i.e., values of triglyceride up to 500 mg/dl, there is close correspondence between total and LDL apo B, with the latter more than 90% of the former. VLDL composition was also examined and two patterns found in hypertriglyceridemic patients: those with normal apo B had markedly lipid enriched VLDL while those with elevated apo B had VLDL which was normal in composition except for a moderate increase in triglyceride content. Thus total apo B within the circumstances studied reflects principally LDL apo B. Moreover measurement of apo B allows distinction between two different forms of hypertriglyceridemia, only one of which - that with an increased LDL particle number - has previous work shown to be associated with increased coronary risk. Total apo B, therefore, provides additional information not available from conventional plasma and lipoprotein lipids which allows more precise physiologic classification and may lead to more rational choice of pharmacologic therapy in normolipidemic and hypertriglyceridemic patients.

Apolipoproteins B↗
PubMed1989

Long-term stepwise sustained improvement in left ventricular ejection fraction after myocardial infarction.

Radionuclide left ventricular ejection fraction, end-diastolic volume, and exercise capacity were determined in 34 selected patients who survived a first Q wave anterior infarction. Patients were included in the study if they had no subsequent cardiac events (unstable angina or myocardial infarction) during the average follow-up period of 47 months (range = 36 to 70 months); none was treated with thrombolysis, coronary angioplasty, or bypass grafting. Overall, mean left ventricular ejection fraction increased from 28 +/- 10% 1 month after infarction to 33 +/- 10% at 3 years (p less than 0.01); mean end-diastolic volume decreased from 217 +/- 99 ml to 171 +/- 80 ml (p less than 0.002). Stepwise improvement in left ventricular ejection fraction occurred in 15 of these patients (group B) and was associated with a significant increase in exercise capacity. Mean ejection fraction in group B was 26 +/- 7% at 1 month and 41 +/- 10% at 3 years (p less than 0.001). In all of these patients there was improved regional wall motion in the noninfarct zone, whereas five patients also showed improvement in the infarct zone. The results indicate a progressive improvement in left ventricular function that occurs over time in some patients after first Q wave anterior infarction, independent of intervention.

Adult↗
PubMed1989

Prognosis in patients with low left ventricular ejection fraction after myocardial infarction. Importance of exercise capacity.

The measurement of left ventricular ejection fraction (LVEF) plays a key role in many strategies for managing patients after acute myocardial infarction. We tested the hypothesis that exercise capacity 1 month after myocardial infarction provides additional information in patients with a low LVEF and therefore assists in risk stratification. One hundred fifteen patients, with documented myocardial infarction and LVEF less than 35% by gated radionuclide scan 1 month after acute myocardial infarction, were followed up for 2 months to 7 years. Exercise capacity was estimated from a treadmill test 1 month after infarction. Using the Cox proportional hazards model, exercise capacity was a significant predictor of death or reinfarction. The relative risk of death, based on a comparison between the lowermost quintile (less than 4 METS) and uppermost quintile (greater than 7 METS), was 3.5 (95% confidence interval, 1.1-9.7); the relative risk in the fourth, third, and second quintile was 2.7, 2.1, and 1.6, respectively. In a multivariate analysis, the observed effect of a good exercise capacity was independent of LVEF. These data indicate that in patients with a low LVEF after myocardial infarction, useful prognostic information can be obtained from exercise testing.

Exercise↗
PubMed1989

Metabolic response of Acylation Stimulating Protein to an oral fat load.

Acylation Stimulating Protein (ASP) is a small (mol wt 14,000), basic (pI 9.0) protein present in human plasma. When examined in vitro with normal human cultured skin fibroblasts and adipocytes, ASP appears to be the most potent stimulant of triglyceride synthesis yet described. In this study, a competitive ELISA assay for ASP has been developed using immunospecific polyclonal antibodies, and ASP levels have been measured in seven normal subjects. Following an oral fat load, a sustained significant increase in ASP occurs, whereas after an oral glucose load, ASP levels do not change significantly. These responses are entirely opposite to those of insulin, which rises sharply but transiently after an oral glucose load but is unchanged after an oral fat load. Both the fasting and peak ASP levels were significantly related to the postprandial lipemia. These data provide the first in vivo evidence that Acylation Stimulating Protein may play an important physiological role in the normal response to an oral fat load.

Adult↗
PubMed1988

Adipose tissue glyceride synthesis in patients with hyperapobetalipoproteinemia.

Adipose tissue was obtained at thoracotomy in five control patients with valvular heart disease, all of whom were free of coronary artery disease and all of whom were normolipidemic with normal low density lipoprotein apolipoprotein B levels, and eight patients with coronary artery disease, all of whom had hyperapobetalipoproteinemia. In both groups, the rates at which linoleic acid and palmitic acid were incorporated into diglyceride and triglyceride were determined in vitro. The data indicate that fatty acid incorporation into adipose tissue glycerides was twice as rapid in controls as in patients with hyperapobetalipoproteinemia. By contrast there was no difference between the groups in the rate of net lipolysis of adipocyte glyceride. The data at hand do not establish the mechanism responsible for the difference in synthesis between normal subjects and patients with hyperapobetalipoproteinemia, but this may explain the delayed chylomicron triglyceride clearance previously observed in the disorder.

Adipose Tissue↗
PubMed1988

Stiff left atrial syndrome.

A 67-year-old female presented seven years after insertion of a mitral prosthesis with mild to moderate pulmonary edema and severe right heart failure with pulmonary and tricuspid insufficiency. Clinical examination and noninvasive tests did not demonstrate prosthetic valve dysfunction. Cardiac catheterization revealed a marked V wave but no mitral regurgitation and no significant mitral diastolic gradient. A clinical diagnosis of a stiff left atrium was made and confirmed at autopsy. The pathophysiology of the syndrome is discussed.

Aged↗
PubMed1988

An angiographic study of ischemia as a determinant of neovascularization in arteriovenous reversal.

The results of recent studies by ourselves and others have demonstrated the feasibility of revascularizing severely ischemic limbs by means of staged arteriovenous reversal at the popliteal level. The results of investigations we did, both clinically and in an animal model, revealed the development of an intense vascular network in the region of the arteriovenous anastomosis as an important component of the revascularization process. To determine the role of ischemia in this process, four groups consisting of three dogs each underwent a popliteal artery to vein anastomosis. In group I, there was no ischemia; group II, distal ischemia only; group III, partial ischemia, and group IV, total ischemia. Angiography at four weeks in all dogs demonstrated that the intense neovascular network seen in previous studies developed only in the limbs of the dogs in group IV. We conclude that the neovascular process seen after creation of arteriovenous reversal develops as a response to severe ischemia. Further studies are needed to better characterize the nature of these vessels, and it is our hope that, in doing so, means of enhancing development of these vessels in order to indirectly revascularize otherwise unsalvagable extremities will be realized.

Animals↗
PubMed1988

Pediatric hyperlipoproteinemia: the phenotypic expression of hyperapobetalipoproteinemia in young probands and their parents.

These data on families of pediatric probands with the hyperapoB phenotype confirm and extend our previous findings of familial aggregation of hyperapoB and document further the expression of hyperapoB in the pediatric age group (Sniderman et al, 1985). In agreement with a more recent report (Beaty et al, 1986) the data suggest, but do not prove, the presence of a Mendelian dominant trait for hyperapoB. The observation that most of the parents affected with hyperapoB were normolipidemic clearly suggests a difference between the expression of hyperapoB in these families and FCH. Further studies on the basic biochemical and genetic defect(s) underlying these common disorders associated with CHD will be necessary to provide a better understanding of the pathogenesis of these important lipoprotein disorders. A significant proportion of children referred to a Lipid Clinic for suspected hyperlipidemia or because of a family history of premature CHD may have hyperapoB. We suggest that measurement of plasma LDL B be added to the standard measurements of lipids and lipoproteins made in Lipid Clinics and that further studies be performed on the utility of using the ratio of LDL C/B as a useful clinical tool to differentiate between those patients with hyperapoB and those with more conventional type II hyperlipoproteinemia.

Adolescent↗