Search PubMed⌕ Search

Biomedical subjects

P Alaupovic

Publications and source records attributed to P Alaupovic.

At least 19 recordsLinked to original sources
PubMed1995

Compensatory vascular changes of remote coronary segments in response to lesion progression as observed by sequential angiography from a controlled clinical trial.

BACKGROUND: Local coronary artery enlargement to compensate for atherosclerotic plaques preserves the vessel lumen. The extent to which coronary segments remote from progressing lesions enlarge is unknown. This is clinically relevant since compensatory enlargement may be important in determining whether clinical complications result from progression of coronary artery disease (CAD). Additionally, compensatory change has implications for quantitative coronary angiographic (QCA) trials, since the effect of progression on diameter means may be mitigated by compensatory changes in remote coronary segments when QCA change is averaged over all lesions. METHODS AND RESULTS: Serial QCA data from 78 subjects in the Monitored Atherosclerosis Regression Study were used to demonstrate compensatory changes in coronary segments remote from progressing or regressing lesions. Coronary segments were first classified as progressing (regressing) if percent diameter stenosis (PS) increased or decreased by > 10 with a concurrent decrease or increase in minimum lumen diameter (MLD) of either > 0.32 mm or > 10% of the normal baseline reference diameter (DNORM). Segments not meeting these criteria were labeled stenosis stable. Stenosis-stable segments opposite progressing lesions showed increases in MLD (P = .0006), DNORM (P = .001), and average diameter (P = .001). On-trial apolipoprotein (apo) B, apo C-III, and blood pressure levels inversely correlated with these compensatory changes. CONCLUSIONS: Lesion progression in one coronary segment is associated with significant increases in segmental diameter of remote parts of the coronary tree. We hypothesize these increases to be vascular compensatory changes in response to progression of CAD. Vascular compensatory change is enhanced by LDL cholesterol and triglyceride-rich lipoprotein reduction and appears to be part of the treatment effect itself.

Adult↗
PubMed1992

Isolation and partial characterization of lipoprotein A-II (LP-A-II) particles of human plasma.

High density lipoproteins (HDL) consist of a mixture of chemically and functionally distinct families of particles defined by their characteristic apolipoprotein (Apo) composition. The two major lipoprotein families are lipoprotein A-I (LP-A-I) and lipoprotein A-I:A-II (LP-A-I:A-II). This study describes the isolation of a third minor HDL family of particles referred to as lipoprotein A-II (LP-A-II) because it lacks ApoA-I and contains ApoA-II as its main or sole apolipoprotein constituent. Because ApoA-II is an integral protein constituent of three distinct lipoprotein families (LP-A-I:A-II, LP-A-II: B:C:D:E and LP-A-II), LP-A-II particles were isolated from whole plasma by sequential immunoaffinity chromatography on immunosorbers with antisera to ApoA-II, ApoB and ApoA-I, respectively. In normolipidemic subjects, the concentration of LP-A-II particles, based on ApoA-II content, is 4-18 mg/dl accounting for 5-20% of the total ApoA-II not associated with ApoB-containing lipoproteins. The lipid composition of LP-A-II particles is characterized by low percentage of triglycerides and cholesterol esters and a high percentage of phospholipids in comparison with lipid composition of LP-A-I and LP-A-II: A-II. The major part of LP-A-II particles contain ApoA-II as the sole apolipoprotein constituent; however, small subsets of LP-A-II particles may also contain ApoD and other minor apolipoproteins. The lipid/protein ratio of LP-A-II is higher than those of LP-A-I and LP-A-I:A-II. In homozygous ApoA-I and ApoA-I/ApoC-III deficiencies, LP-A-II particles are the only ApoA-containing high density lipoprotein with levels found to be within the same range (7-13 mg/dl) as those of normolipidemic subjects. However, in contrast to normal LP-A-II, their lipid composition is characterized by higher percentages of triglycerides and cholesterol esters and a lower percentage of phospholipids and their apolipoprotein composition by the presence of ApoC-peptides and ApoE in addition to ApoA-II and ApoD. These results show that LP-A-II particles are a minor HDL family and suggest that, in the absence of ApoA-I-containing lipoproteins, they become an efficient acceptor/donor of ApoC-peptides and ApoE required for a normal metabolism of triglyceride-rich lipoproteins. Their other possible functional roles in lipid transport remain to be established in future experiments.

Apolipoprotein A-I↗
PubMed1992

Lipoprotein abnormalities in hirsute women. II. Compensatory responses of insulin resistance and dehydroepiandrosterone sulfate with obesity.

OBJECTIVE: The purpose of our study was to further understand interrelationships between insulin, androgens, obesity, and apolipoprotein metabolism. STUDY DESIGN: In this University cross-sectional observational study for hypothesis generation, 53 women with hirsutism-hyperandrogenism were ternately divided according to body mass index into the following groups: 22 to 28 (n = 17), 29 to 36 (n = 19), 37 to 61 (n = 17), and 16 controls. Mean hormone and clinical parameters were compared by using the Student t test, analysis of variance, and Pearson correlation. RESULTS: Dehydroepiandrosterone sulfate correlated negatively with fasting insulin (r = 0.4, p < 0.05) and reached significance in those most obese. Unbound testosterone concentrations were 24.7, 38.9, and 31.9 ng/dl, respectively. Dehydroepiandrosterone sulfate concentrations were 2.8, 2.3, and 2.3 micrograms/dl, respectively; their ratios were 13.4, 18.6, and 20.4, respectively, even though mean fasting insulin concentrations (reflecting insulin resistance) were 13.0, 20.4, and 42.6 microU/ml, respectively. Although more atherogenic apolipoprotein profiles and higher fasting insulin concentrations were found with greater body weight, lipid-insulin interrelationships may reflect dehydroepiandrosterone sulfate interaction. CONCLUSIONS: We hypothesize that dehydroepiandrosterone sulfate dampens the effect of insulin resistance, which in turn is reflected in apolipoprotein profiles in women with hirsutism/hyperandrogenism.

Adaptation, Physiological↗
PubMed1992

Apolipoprotein A-I and apolipoprotein B containing lipoprotein particles in coronary patients treated with extracorporal low density lipoprotein precipitation (HELP).

Evidence for chemical and biological heterogeneity of human plasma lipoprotein density classes has been steadily accumulating over the last 15 years. Furthermore, several recent reports have indicated potential clinical significance of certain lipoprotein subspecies as either atherogenic or antiatherogenic. It is generally accepted that lipid lowering treatments can retard or even reverse development of atherosclerotic lesions. However, very little is known about effects of various lipid lowering treatments on specific lipoprotein particles. The purpose of this study was to explore the effects of heparin induced extracorporal low density lipoprotein precipitation (HELP) on various subspecies of plasma lipoprotein particles defined primarily by their apolipoprotein composition. Using particle specific enzyme immunoassays, the immediate changes in lipoprotein particle profiles were analyzed after a single HELP treatment in 12 patients with angiographically documented coronary artery disease. In a separate group of 6 patients, particles were repeatedly measured over a period of 96 h following a HELP treatment. Single HELP treatment caused an immediate and highly significant decrease (67%) in the concentration of simple lipoprotein particles containing apolipoprotein B (apo B) as a sole apolipoprotein (LP-B). Various subspecies of complex particles containing apo B and other apolipoproteins (Lp-B-complex) were also decreased although to a lesser degree (44-53%). HELP treatment caused an insignificant, 3% decrease of lipoprotein particles containing apo A-I but no apo A-II (Lp-A-I) and a 6% decrease in the concentration of particles containing both apo A-I and apo A-II (Lp-A-I:A-II). During the 96-h period following HELP treatment various apo B containing particles recovered at different rates in different patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Apolipoprotein A-I↗
PubMed1992

Lipid and apolipoprotein abnormalities in hirsute women. I. The association with insulin resistance.

OBJECTIVE: We attempted to evaluate apolipoprotein lipid levels in hirsute hyperandrogenic women and to clarify the influence of insulin resistance versus endogenous sex steroids on these profiles. STUDY DESIGN: Forty-seven women seen for evaluation of hirsutism in the Reproductive Endocrine Clinic were contrasted with 15 normal women. Thirty-one patients were treated with the gonadotropin-releasing hormone analog, leuprolide acetate, 7.5 mg intramuscularly monthly for 3 months. Insulin resistance was assessed before and after GnRH analog administration. Mean concentrations were compared with the Student t test and analysis of variance. RESULTS: Hirsute women were heavier and had higher systolic and diastolic blood pressures, more menstrual irregularities (all p less than 0.01), and higher waist/hip ratios (p less than 0.05). They had higher triglyceride, very-low-density lipoprotein C-III levels and lower high-density lipoprotein cholesterol concentrations (all p less than 0.01). They had lower apolipoprotein A-I/A-II ratios (p less than 0.01). After administration of GnRH analog, androgen and estrogens were suppressed and insulin resistance was unaltered. Insulin correlated with apolipoprotein lipid abnormalities. CONCLUSION: Lipid and apolipoprotein abnormalities in these hirsute women seem to be associated more with insulin resistance than with endogenous androgens or estrogens.

Adult↗
PubMed1992

Dyslipoproteinemia in diabetic renal failure.

Plasma concentrations of lipids and apolipoproteins (Apo) were determined in 34 patients with long-standing type I (insulin-dependent) diabetes mellitus. Twenty-four patients had renal insufficiency (GFR 4 to 55 ml/min) due to diabetic nephropathy, while 10 patients had no clinical signs of nephropathy. Results were compared with those in 42 non-diabetic patients with comparable degree of renal insufficiency and with asymptomatic control subjects. Diabetic patients without nephropathy had plasma lipid and apolipoprotein concentrations similar to those of the control subjects. Diabetic patients with renal insufficiency had a significant increase in triglycerides (TG) and, to a lesser extent, in total cholesterol (TC). The patients also had reduced levels of ApoA-I and ApoA-II, increased levels of ApoC-II and ApoC-III, while increases in levels of ApoB and ApoE were statistically significant in patients with GFR < 20 ml/min. These lipids and apolipoprotein abnormalities were accentuated with decreasing renal function. The reduction in the ApoA-I/ApoC-III ratio characteristic of renal insufficiency was found in normo- and hyper-TG diabetic patients with nephropathy; this ratio was correlated with the GFR levels. Patients with higher HbA1C values had higher levels of ApoC-II and ApoC-III. The findings in the diabetic patients corresponded with those in non-diabetic patients with renal insufficiency. However, diabetic patients had higher ApoC-III and ApoE levels. The abnormalities of lipid metabolism in diabetic renal insufficiency seem to reflect primarily metabolic impairments characteristic of renal insufficiency, but may be further accentuated by the diabetic state and the metabolic control.

Adult↗
PubMed1992

Identification of apoB-containing lipoprotein families in NIDDM.

The purpose of this study was to determine the concentrations and composition of apoB-containing lipoprotein families in whole plasma and major lipoprotein density classes of a selected group of Native Americans from northeastern Oklahoma with non-insulin-dependent diabetes mellitus. The measurement of lipoprotein density classes showed that the total lipoprotein mass of very-low-density lipoproteins was significantly higher and that of high-density lipoproteins significantly lower in diabetic patients than nondiabetic control subjects regardless of their plasma triglyceride levels. The VLDLs were enriched with TG, free cholesterol, and apolipoproteins C-III and E. HDLs were enriched with TG but depleted of apoC-III and apoE. There was no change in the levels of TG-enriched low-density lipoproteins. Fractionation of VLDL by sequential immunoprecipitation with antisera to apoE and apoC-III established that increased concentrations of this density class in diabetic patients are due to elevated levels of TG-rich lipoprotein LP-B:C and lipoprotein LP-B:C:E. The levels of LP-B:C particles were increased more than the levels of LP-B:C:E particles. The LDLs were characterized by a slight increase in TG-enriched lipoprotein B and no change in the levels of LP-B:C and LP-B:C:E. There was no difference between diabetic patients with or without vascular disease in the levels of LP-B and LP-B:C:E. However, patients with vascular disease had higher concentrations of LP-B:C particles in VLDL and whole plasma than patients without vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Increased concentrations of Apo B-containing triglyceride-rich lipoprotein particles in patients with chronic renal failure.

The dyslipoproteinemia of chronic renal failure (CRF) was characterized by discrete Apo B-containing lipoprotein particles separated by sequential immunoprecipitation of VLDL, IDL and LDL with antisera to Apo E and Apo C-III. CRF patients before and during dialysis had increased concentrations of Apo B-containing lipoproteins (LP) due to increased levels of triglyceride-rich LP-B:C and LP-B:C:E particles with no significant change in the levels of cholesterol-rich LP-B. Patients on hemodialysis had lower concentrations of LP-B:C and higher concentrations of LP-B:C:E than predialytic patients. The increase of Apo B-containing lipoprotein particles in CRF may contribute to atherosclerotic vascular disease and to glomerulosclerosis and progression of renal insufficiency.

Adult↗
PubMed1991

Lipid and apolipoprotein profiles of uremic dyslipoproteinemia--relation to renal function and dialysis.

To study the effect of renal function on the development of lipid and apolipoprotein abnormalities in human renal disease, we have investigated 75 patients at different stages of renal insufficiency. The patient population consisted of 19 patients with less advanced renal failure (CRF:1) characterized by a mean glomerular filtration rate (GFR) of 37.4 +/- 14 ml/min, 31 patients with advanced renal failure (CRF:2) having a mean GFR value of 7.9 +/- 7.3 ml/min and 25 patients on maintenance hemodialysis (CRF:HD). Patients in the CRF:1 group had normal plasma triglyceride (TG) and total cholesterol (TC) levels. In the CRF:2 and CRF:HD group, TG levels were increased two- to threefold, together with a moderate elevation of TC levels. All patient groups had elevated levels of VLDL cholesterol and slightly decreased levels of HDL cholesterol. The apolipoprotein profile of all patient groups was characterized by significantly reduced levels of apolipoprotein (Apo)A-I and ApoA-II and significantly increased levels of ApoC-III. CRF:2 and CRF:HD patients had also moderately elevated levels of ApoB, ApoC-I and ApoC-II. Levels of ApoE were only elevated in CRF:HD patients. All patients, regardless of TG levels, had significantly lower ApoA-I/ApoC-III ratios than controls. GFR was positively correlated with ApoA-I and inversely correlated with TC, TG and ApoC-III. CRF:HD patients had slightly higher ApoA-I and ApoA-II and lower ApoB levels compared to CRF:2 patients. Patients with vascular disease had higher TC, TG, ApoB, ApoC-II and ApoE than patients without vascular disease. These results demonstrate that the dyslipoproteinemia with CRF is already manifested at the early stages of disease through its abnormal apolipoprotein rather than lipid profile.

Adult↗
PubMed1991

Composition of plasma ApoA-I-containing lipoprotein particles in children and adults.

The purpose of this study was to examine sex- and age-related differences in the concentration and composition of lipoprotein particles containing apoA-I (LP-A-I) and those containing apoA-I and apoA-II (LP-I:A-II), the main HDL as defined by their apolipoprotein composition. Lipoproteins were isolated by immunoaffinity chromatography of whole plasma from 16 normal prepubertal children and 15 normal male and female adults using "pan"-MAb to apoA-I and apoA-II. Although there was no difference between children and adults in the concentration of LP-A-I:A-II, adult females had significantly higher levels of LP-A-I than either children or adult males. Main differences between children and adults as well as between adult males and females were in the apolipoprotein composition of the lipoprotein particles; children had the highest content of minor apolipoproteins (apoC and apoE) in LP-A-I but the lowest in LP-A-I:A-II. The lipid/apolipoprotein ratios of LP-A-I and LP-A-I:A-II were significantly higher in children and women than in men. The LP-A-I and LP-A-I:A-II contained 75% of the total plasma apoC and apoE in women and children but only 50% in men. However, in all three groups, 70-90% of the minor HDL apolipoproteins were associated with LP-A-I:A-II. The nonmolar ratios of minor apolipoproteins in LP-A-I and LP-A-I:A-II and the sex- and age-related differences in apoA-I/apoA-II ratios of LP-A-I:A-II suggest that both lipoproteins may consist of a spectrum of lipoprotein subfamilies differing in their apolipoprotein composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Characterization of apoA- and apoB-containing lipoprotein particles in a variant of familial apoA-I deficiency with planar xanthoma: the metabolic significance of LP-A-II particles.

This study describes a variant of familial apoA-I deficiency associated with a moderate risk for premature coronary artery disease. The proband, a 25-year-old man of Philippine origin, and his 62-year-old maternal aunt had peripheral corneal opacification, xanthelasma, and planar xanthoma; the aunt had coronary artery bypass surgery at 61 years of age. Proband's parents and three brothers were asymptomatic and apparently healthy. The characteristic apolipoprotein features of affected patients were the immunochemically and chemically undetectable apoA-I, reduced levels of apoA-II, apoC-II, apoC-III, and apoD, and normal levels of apoB and apoE; except for negligible levels of high density lipoprotein (HDL)-cholesterol (2-3 mg/dl), their plasma lipid profile was normal. The apoA-I levels in all five unaffected relatives were more than one SD below the normal mean values for their age and sex; the HDL-cholesterol levels of proband's unaffected brothers were below the 10th percentile of normal control values. Patient's very low density lipoprotein (VLDL), low density lipoprotein (LDL), and HDL contained 1.4, 80.4, and 18.1%, whereas those of control subjects contained 2.7, 28.8, and 68.1% of the total apolipoprotein mass, respectively. In unaffected relatives, the levels of LP-A-I, but not LP-A-I:A-II, were significantly lower than in controls. Neither of the two patients had detectable concentrations of LP-A-I or LP-A-I:A-II. Their HDL only consisted of LP-A-II particles, the levels of which (7-13 mg/dl) were similar to those of unaffected relatives or controls. There was no difference in the lipid composition of LP-A-II between patients and their relatives. However, LP-A-II from patients contained substantial amounts of apoC-peptides and apoE (0.40-0.98 mg/mg apoA-II), whereas those from unaffected relatives were free of these minor apolipoproteins. In patients, among all four major apoB-containing lipoproteins, only the levels of LP-B and LP-B:C were slightly higher than those in controls. Results of this study suggest a genetic cause for this variant of apoA-I deficiency characterized most probably by autosomal recessive inheritance. It appears that patients are likely to be homozygous for a gene present in single dose in the parents and brothers of the affected proband.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗