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Biomedical subjects

F Hoppichler

Publications and source records attributed to F Hoppichler.

At least 37 records · Page 2Linked to original sources
PubMed1996

Apolipoprotein(a) kringle IV repeat number predicts risk for coronary heart disease.

A high plasma concentration of lipoprotein(a) [Lp(a)] has been suggested as a risk factor for coronary heart disease (CHD), but some recent prospective studies have questioned the significance of Lp(a). Lp(a) concentrations are determined to a large extent by the hypervariable apo(a) gene locus on chromosome 6q2.7, which contains a variable number of identical tandemly arranged transcribed kringle IV type 2 repeats. The number of these repeats correlates inversely with plasma Lp(a) concentration. We analyzed whether apo(a) gene variation (kringle IV repeat number) is associated with CHD. Apo(a) genotypes were determined by pulsed-field gel electrophoresis/genomic blotting in CHD patients who had undergone angiography (n = 69) and control subjects matched for age, sex, and ethnicity (n = 69) and were related to Lp(a) concentration, apo(a) isoform in plasma, and disease status. Apo(a) alleles with a low kringle IV copy number ( < 22) and high Lp(a) concentration were significantly more frequent in the CHD group (P < .001), whereas large nonexpressed alleles were more frequent in control subjects. The odds ratio for CHD increased continuously with a decreasing number of kringle IV repeats and ranged from 0.3 in individuals with > 25 kringle IV repeats on both alleles to 4.6 in those with < 20 repeats on at least one allele. This provides direct genetic evidence that variation at the apo(a) gene locus, which determines Lp(a) levels, is also a determinant of CHD risk.

Alleles↗
PubMed1995

Thyroid hormone (fT4) reduces lipoprotein(a) plasma levels.

To study the influence of thyroid hormone on Lp(a) plasma concentration we measured Lp(a), total cholesterol, LDL-C, HDL-C, triglycerides and fT4 levels and determined apo(a) phenotypes in 26 patients with hyperthyroidism in a follow-up study before and after thyreostatic treatment. The pretreatment values of total cholesterol (TC), LDL-C, and Lp(a) were significantly reduced as compared with those of healthy controls. The reduced mean Lp(a) concentrations could not be explained by a difference of apo(a) 'size allele' frequencies between patients and controls. During thyreostatic treatment mean concentrations of TC, LDL-C, and HDL-C increased significantly. The mean Lp(a) value was not changed after 4 weeks of treatment. The individual changes of Lp(a), however, correlated significantly with those of LDL-C levels (R = 0.40, P = 0.04). Eighty-one per cent of the patients showed an increase of Lp(a) or no change of the Lp(a) level and 19% reacted with a decrease upon thyreostatic treatment. The observed lipid and lipoprotein changes were not different in patients with Graves disease or multifocal toxic goiter. The results indicate that Lp(a) plasma levels are decreased in the hyperthyroid state irrespective of the pathogenic mechanism.

Adolescent↗
PubMed1994

The immunosuppressive substance 2-chloro-2-deoxyadenosine modulates lipoprotein metabolism in a murine macrophage cell line (P388 cells).

A recently developed immunosuppressive substance, 2-chloro-2-deoxyadenosine (2-CdA), was reported to inhibit monocyte functions at low concentration. Because macrophages play a key role in the formation of atherosclerotic plaques, it was of interest to study the effect of 2-CdA on cellular lipid metabolism. For this purpose we have used a macrophage cell line (P388) to perform incubation studies in the presence of acetylated low density lipoprotein (Ac-LDL) and 2-CdA. The addition of 2-CdA, in concentrations ranging from 5-20 nM, induced a dose-dependent decrease in cellular cholesterol content and in the amount of extracellular [14C]oleic acid (OA) incorporated into the cholesteryl ester (CE) fraction. The effect was maximized at 20 nM 2-CdA with an 86% reduction in cholesterol esterification compared to controls (P < 0.008). To evaluate the mechanism of interaction of 2-CdA with cellular lipid metabolism, deoxycytidine (dCyt) and 3-methoxybenzamide (3-MOB), substances known to antagonize the effect of 2-CdA in different ways, were co-administered with 2-CdA. dCyt, a competitive inhibitor of dCyt kinase, which catalyzes phosphorylation to the active metabolite, antagonized the effects of 20 nM 2-CdA, producing significantly greater incorporation of extracellular [14C]OA into the CE fraction than in the presence of 2-CdA alone (P < 0.0086). Co-incubation with 2-CdA and the poly-ADP-ribose synthetase inhibitor 3-MOB, which is known to render cells resistant to 2-CdA toxicity by preventing cellular nicotinamide adenine dinucleotide (NAD)- and adenosine triphosphase-depletion, also reversed the effect of 2-CdA on lipid accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1994

Low-density lipoproteins of the postprandial state induce cellular cholesteryl ester accumulation in macrophages.

Chemically or biologically modified low-density lipoproteins (LDL) but not native unmodified LDL lead to foam cell formation in monocyte-derived macrophages. Since the magnitude of postprandial lipemia after a challenge test seems to be associated with coronary artery disease, we tested the hypothesis that in the course of postprandial lipemia, LDL appear in plasma that are capable of leading to foam cell formation even without prior modification. We incubated the macrophage-like cell line P388 with unmodified postabsorptive and postprandial LDL from 17 healthy donors and measured the cellular cholesterol and triglyceride contents and amounts of exogenous [14C]oleic acid incorporated into the cholesteryl ester fraction. Postprandial LDL induced a significantly more pronounced cholesteryl ester accumulation than did postabsorptive LDL (477 +/- 286% versus 212 +/- 173%, respectively; P < .003). The increase in cellular total cholesterol was significantly higher as a result of cell incubation with postprandial LDL (107 +/- 61%) than with postabsorptive LDL (54 +/- 40%, P < .003), whereas no increase in triglyceride content was observed (P < .589) in either case. After CuSO4 incubation and incubation with P388 cells, postprandial LDL revealed more thiobarbituric acid-reacting substances than did postabsorptive LDL (55 +/- 10 versus 28 +/- 9 nmol/mg protein, P < .018; 28 +/- 4 versus 20 +/- 3 nmol/mg protein). The increase in cellular cholesteryl ester synthesis caused by postprandial LDL was reduced by more than 50% when lipoproteins and cells were incubated in the presence of ascorbic acid (P < .007).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Hypertriglyceridemia and acute pancreatitis].

Data of 26 patients suffering from severe pancreatitis, who were treated at the anesthesiologic intensive care unit during the years 1991 and 1992, were evaluated with respect to etiologic factors, especially hypertriglyceridemia, stage of the disease and clinical outcome. Hypertriglyceridemia was found in 13 cases (11 men, 2 women, mean age 42 +/- 9 years) with values between 330 mg/dl and 4000 mg/dl. Lipid electrophoresis revealed a pattern typical for type IV hyperlipidemia. Insulin dependent diabetes was present in 4 patients and 5 reported about an unusual high alcohol intake preceding pancreatitis. Beside surgical approaches, including drainage and lavage, and basic intensive care treatment plasmapheresis was performed in 8 patients with hypertriglyceridemia. 5 patients with pancreatitis and hypertriglyceridemia died out of multiorganic failure, and so the mortality rate was 38%. The group of patients with pancreatitis caused by cholelithiasis or chronic alcohol consumption showed a mortality rate of 46%. The poor outcome of pancreatitis associated with hypertriglyceridemia demonstrates the importance of the treatment of hypertriglyceridemia in order to prevent the development of pancreatitis. The determination of plasma triglyceride values should belong to the routine diagnostic procedures in acute pancreatitis.

Acute Disease↗
PubMed1993

Elevated plasma concentrations of lipoprotein(a) in patients with end-stage renal disease are not related to the size polymorphism of apolipoprotein(a).

Patients with terminal renal insufficiency suffer from an increased incidence of atherosclerotic diseases. Elevated plasma concentrations of lipoprotein(a) [Lp(a)] have been established as a genetically controlled risk factor for these diseases. Variable alleles at the apo(a) gene locus determine to a large extent the Lp(a) concentration in the general population. In addition, other genetic and nongenetic factors also contribute to the plasma concentrations of Lp(a). We therefore investigated Apo(a) phenotypes and Lp(a) plasma concentrations in a large group of patients with end-stage renal disease (ESRD) and in a control group. Lp(a) concentrations were significantly elevated in ESRD patients (20.1 +/- 20.3 mg/dl) as compared with the controls (12.1 +/- 15.5 mg/dl, P < 0.001). However, no difference was found in apo(a) isoform frequency between the ESRD group and the controls. Interestingly, only patients with large size apo(a) isoforms exhibited two- to fourfold elevated levels of Lp(a), whereas the small-size isoforms had similar concentrations in ESRD patients and controls. Beside elevated Lp(a) concentrations, ESRD patients had lower levels of plasma cholesterol and apolipoprotein B. These results show that elevated Lp(a) plasma levels might significantly contribute to the risk for atherosclerotic diseases in ESRD. They further indicate that nongenetic factors related to renal insufficiency or other genes beside the apo(a) structural gene locus must be responsible for the high Lp(a) levels.

Adult↗
PubMed1992

Apo(a) isoforms predict risk for coronary heart disease. A study in six populations.

Elevated concentrations of lipoprotein(a) (Lp[a]) in plasma are associated with premature coronary heart disease (CHD). Lp(a) levels are largely determined by alleles at the hypervariable apolipoprotein(a) (apo[a]) gene locus, but other genetic and environmental factors as well as diseases also affect plasma Lp(a) concentrations. It is therefore unclear whether Lp(a) is a primary genetic risk factor or whether Lp(a) levels are elevated secondary to disease in CHD patients. We have analyzed apo(a) phenotypes that represent a stable genetic trait in subjects with CHD and control subjects from different populations representing a variety of ethnic groups (Tyrol, Germany, Wales, Israel, Singapore Chinese, and Singapore Indian). Despite differences in sampling design and disease definition in this multipopulation case-control study, those apo(a) isoforms associated with high Lp(a) plasma concentrations (B, S1, and S2) were more frequent in the CHD patients in each ethnic group. These differences were significant in three of the studied populations and highly significant (p < 0.001) in the pooled (total) group. Lp(a) concentrations were also measured in all groups except Germans and were found to be consistently higher in cases than in control subjects in each ethnic group. For all but one population (Israeli) the differences were significant. The effects of the apo(a) size polymorphism on Lp(a) levels were similar in CHD patients and control subjects from different populations. The data demonstrate that alleles at the apo(a) locus determine the risk for CHD through their effects on Lp(a) concentrations across multiple populations with large differences in CHD frequency and risk factor profiles.

Adult↗
PubMed1992

[Snuff aspiration as a cause of recurrent pulmonary infiltrations in a 60-year-old patient with chronic renal failure].

Pulmonary infiltrations associated with renal failure demand several diagnostic procedures to exclude autoimmune disorders affecting both organ systems or to find an infectious cause of the disease. We report the case of a 60 year-old man with chronic renal failure and recurring pulmonary infiltrations. On admission to hospital all diagnostic parameters for systemic vasculitis, infectious or neoplastic disease were negative, including the histological report on transbronchial biopsies. Eventually, follow-up biopsies taken 3 months later showed vegetable fibres and necrosis due to intensive snuff abuse during the previous months. After the patient stopped taking snuff the pulmonary infiltrations improved quickly. Uraemic neuropathy, which may have facilitated aspiration, as well as the reduced pulmonary and systemic defence mechanisms due to chronic renal failure probably contributed to a considerable degree to the development of pulmonary infiltration.

Biopsy↗
PubMed1992

[Pravastatin, a new cholesterol synthesis inhibitor for lowering increased serum cholesterol].

The association between increased risk for coronary artery disease (CAD) and elevated plasma cholesterol has been firmly established. The beneficial effect of cholesterol lowering treatment modalities was confirmed in both primary and secondary intervention trials. Because long-term treatment is usually required for lipid lowering therapies the drugs used for lipid reduction have to be not only efficacious but also safe. Inhibitors of cholesterol synthesis that have become clinically available during the last few years, can reduce plasma levels of total cholesterol and low density lipoprotein (LDL)-cholesterol very effectively. In the Familial Atherosclerosis Treatment Study (FATS) an intensive cholesterol lowering treatment modality consisting of a combination of an inhibitor of cholesterol synthesis and colestipol reduced the progression of coronary lesions and caused a partial regression of such lesions. Among the various inhibitors of cholesterol synthesis developed recently, pravastatin appears to be tissue-specific because of its hydrophilic property.

Cholesterol↗
PubMed1990

Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to coronary heart disease in patients with familial hypercholesterolemia.

Familial hypercholesterolemia carries a marked increase in the risk of coronary heart disease (CHD), but there is considerable variation between individuals in susceptibility to CHD. To investigate the possible role of lipoprotein(a) as a risk factor for CHD, we studied the association between serum lipoprotein(a) levels, genetic types of apolipoprotein(a) (which influence lipoprotein(a) levels), and CHD in 115 patients with heterozygous familial hypercholesterolemia. The median lipoprotein(a) level in the 54 patients with CHD was 57 mg per deciliter, which is significantly higher than the corresponding value of 18 mg per deciliter in the 61 patients without CHD. According to discriminant-function analysis, the lipoprotein(a) level was the best discriminator between the two groups (as compared with all other lipid and lipoprotein levels, age, sex, and smoking status). Phenotyping for apolipoprotein(a) was performed in 109 patients. The frequencies of the apolipoprotein(a) phenotypes and alleles differed significantly between the patients with and those without CHD. The allele LpS2, which is associated with high lipoprotein(a) levels, was found more frequently among the patients with CHD (0.33 vs. 0.12). In contrast, the LpS4 allele, which is associated with low lipoprotein(a) levels, was more frequent among those without CHD (0.27 vs. 0.15). We conclude that an elevated level of lipoprotein(a) is a strong risk factor for CHD in patients with familial hypercholesterolemia, and the increase in risk is independent of age, sex, smoking status, and serum levels of total cholesterol, triglyceride, or high-density lipoprotein cholesterol. The higher level of lipoprotein(a) observed in the patients with CHD is the result of genetic influence.

Adult↗
PubMed1990

Abetalipoproteinemia with an ApoB-100-lipoprotein(a) glycoprotein complex in plasma. Indication for an assembly defect.

Patients with autosomal recessive abetalipoproteinemia (ABL) lack in their plasma all lipoproteins containing apolipoprotein (apo)B-100 or B-48. Previous studies have suggested that this is due to the complete absence of apoB. We have investigated whether such patients (n = 10) are able to secrete the lipoprotein(a) (Lp(a] glycoprotein (apo(a] which, in normal plasma, exists as a complex with low density lipoproteins containing apoB-100 (Lp(a) lipoprotein). All 10 patients had reduced but detectable apo(a) levels in plasma (mean, 0.49 mg/dl; range, 0.2-2.03 mg/dl) but no Lp(a) lipoprotein. However, we also detected small amounts (0.2-2.8 mg/dl) of apoB in all patients with ABL. The apoB in the ABL patients had the size of apoB-100 and occurred as a lipid-poor complex with the Lp(a) glycoprotein in a fraction of density 1.22 g/ml. This material may represent partially assembled Lp(a) lipoprotein. There was also uncomplexed apo(a) and apoB-100 in the ABL plasma. The distribution and relative concentration of both proteins in the density fraction greater than 1.06 g/ml varied among patients. The data suggest that in ABL, the assembly of apoB-containing lipoproteins is defective and that apoB-100 may be secreted without its full lipid complement when complexed with apo(a).

Abetalipoproteinemia↗