Activation of phosphatidylinositol-specific phospholipase C by HDL-associated lysosphingolipid. Involvement in mitogenesis but not in cholesterol efflux.

Our earlier studies demonstrated that high-density lipoproteins (HDLs) stimulate multiple signaling pathways, including activation of phosphatidylcholine-specific phospholipases C and D (PC-PLs) and phosphatidylinositol-specific phospholipase C (PI-PLC). However, only activation of PC-PLs was linked to the HDL-induced cholesterol efflux. In the study presented here, the role of HDL-induced PI-PLC activation was studied.

Treatment of hypertriglyceridemia by two diets rich either in unsaturated fatty acids or in carbohydrates: effects on lipoprotein subclasses, lipolytic enzymes, lipid transfer proteins, insulin and leptin.

Background: There is lack of agreement on which dietary regimen is most suitable for treatment of hypertriglyceridemia, especially if high triglyceride concentrations are not due to obesity or alcohol abuse. We compared the effects on blood lipids of a diet high in total and unsaturated fat with a low-fat diet in patients with triglyceride concentrations of > 2.3 mmol/l.

Prevention of coronary heart disease by raising high-density lipoprotein cholesterol?

Consistent with several potentially anti-atherogenic activities of high-density lipoproteins in vitro, low plasma levels of high-density lipoprotein cholesterol are associated with an increased risk of coronary heart disease. In addition to genes, lifestyle factors (e.g.

Primary prevention of coronary heart disease: from controversy to consensus.

In recent years, interest has tended to focus on prevention of coronary events in high-risk groups, particularly those with established coronary heart disease. While this is understandable, it has led to a lack of emphasis on primary prevention. Yet it is only by means of primary or even pri-mordial prevention that a substantial reduction in coronary mortality on a population level will be achieved.

Risk for diabetes mellitus in middle-aged Caucasian male participants of the PROCAM study: implications for the definition of impaired fasting glucose by the American Diabetes Association. Prospective Cardiovascular Münster.

The criteria of the American Diabetes Association and the WHO for the diagnosis of diabetes mellitus are controversially discussed. In a prospective population study, we evaluated the data of 3,737 men, aged 36-60 yr, without diabetes mellitus and with fasting serum glucose levels less than 7 mmol/L at entry into the study who had at least 1 repeat examination during a follow-up of 4-10 yr. During a mean follow-up of 6.

High-density lipoproteins inhibit fibrinogen binding on adenosine diphosphate-activated monocytes.

High levels of fibrinogen and low levels of high-density lipoprotein (HDL) cholesterol were reported to be risk factors for coronary heart disease. CD11b/CD18, a fibrinogen-binding protein, is expressed on the surface of monocytes, which play a crucial role in the formation of atherosclerotic lesions. In the present study, we investigate the effects of antibodies against CD11b and CD18, as well as HDL3 and low-density lipoprotein (LDL) cholesterol on fibrinogen binding on monocytes.

Involvement of phospholipase D in store-operated calcium influx in vascular smooth muscle cells.

In non-excitable cells, sustained intracellular Ca2+ increase critically depends on influx of extracellular Ca2+. Such Ca2+ influx is thought to occur by a 'store-operated' mechanism, i.e.

Endogenous apolipoprotein E modulates cholesterol efflux and cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 and lipid-free apolipoproteins in mouse peritoneal macrophages.

We investigated the effect of endogenous apolipoprotein (apo) E synthesis in mouse peritoneal macrophages on cholesterol efflux and intracellular cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 (HDL3) and lipid-free apolipoproteins (apo). After loading with acetylated LDL (acLDL) peritoneal macrophages from wild-type (apoE(+/+)) and apoE-deficient (apoE(-/-)) mice were incubated with medium alone or with liposomes, HDL3, lipid-free apoA-I, or lipid-free apoE3. Cholesterol and cholesteryl esters in the cells and culture media were quantified by HPLC.

Genotype/phenotype relationships in HNF-4alpha/MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein(a), and triglyceride levels.

Hepatocyte nuclear factor (HNF)-4alpha is a transcription factor that plays an important role in regulation of gene expression in pancreatic beta-cells and in the liver. Heterozygous mutations in the HNF-4alpha gene are responsible for maturity-onset diabetes of the young 1 (MODY1), which is characterized by pancreatic beta-cell-deficient insulin secretion. HNF-4alpha is a major transcriptional regulator of many genes expressed in the liver.

C-reactive protein and the severity of atherosclerosis in myocardial infarction patients with stable angina pectoris.

Background: Recent findings provide evidence for the importance of inflammatory processes in the pathogenesis of atherosclerosis. C-reactive protein was elevated in patients with peripheral artery disease, coronary heart disease and myocardial infarction compared to normal subjects.

Methods: In 1112 male and 299 female survivors of myocardial infarction (mean age +/- SD, men, 50.

Cholesterol efflux from normal and Tangier disease fibroblasts into normal, high-density lipoprotein-deficient, and apolipoprotein E-deficient plasmas.

Tangier disease (TD) fibroblasts have defective cholesterol release in the presence of lipid-free apolipoproteins. We compared normolipidemic probands and patients with apolipoprotein A-I (apoA-I) deficiency, apoE deficiency, or TD in terms of the plasma capacity to induce the efflux of [3H]-cholesterol from normal and TD fibroblasts and to esterify this cell-derived cholesterol. Compared with normal fibroblasts, TD fibroblasts released a significantly smaller fraction of [3H]-cholesterol into normal, high-density lipoprotein (HDL)-deficient, and apoE-deficient plasmas.

D609-phosphatidylcholine-specific phospholipase C inhibitor attenuates thapsigargin-induced sodium influx in human lymphocytes.

Previously, we reported that the phosphatidylcholine-specific phospholipase C (PC-PLC) inhibitor tricyclodecan-9-yl xanthogenate (D609) potentiates thapsigargin-induced Ca(2+) influx in human lymphocytes. In the present study we examined the effect of D609 on the thapsigargin-induced Na(+) entry. We found that the early phase of the thapsigargin-induced increase in the intracellular Na(+) concentration (approx.

[Knowledge about stroke among the German population].

Background And Objective: Modern stroke therapy requires patients to correctly identify stroke symptoms and seek immediate hospital admission. US studies showed that only 57% of the population knew at least one stroke symptom. This is the first study about stroke knowledge among German populations.

Molecular genetics of arrhythmias--a new paradigm.

The molecular genetic background of inherited cardiac arrhythmias has only recently been uncovered. This late development in comparison to other inherited cardiac disorders has partly been due to the high mortality and early disease onset of these arrhythmias resulting in mostly small nucleus families. Thus, traditional genetic linkage studies, which are based on the genetic information obtained from large multi-generation families, were made difficult.

Insulin-like growth factor-binding protein-3 is associated with the presence and extent of coronary arteriosclerosis.

Aging is associated with the progression of arteriosclerosis and the decline of several endocrine functions. We therefore investigated the association of coronary arteriosclerosis with hormones, the serum concentrations of which change during aging. Coronary angiograms of 189 men <70 years old were evaluated by 3 semiquantitative score systems to estimate the extent of focal and diffuse vessel wall alterations.

Insulin-like growth factor-binding protein-3 is associated with the presence and extent of coronary arteriosclerosis.

Aging is associated with the progression of arteriosclerosis and the decline of several endocrine functions. We therefore investigated the association of coronary arteriosclerosis with hormones, the serum concentrations of which change during aging. Coronary angiograms of 189 men <70 years old were evaluated by 3 semiquantitative score systems to estimate the extent of focal and diffuse vessel wall alterations.

Detection of missense mutations in the genes for lipoprotein lipase and hepatic triglyceride lipase in patients with dyslipidemia undergoing coronary angiography.

Coronary events have a close association with a low HDL/hypertriglyceridemia (LHDL/HTG) phenotype. As enzymes that hydrolyze triglyceride-rich lipoproteins are associated with a modulation of both HDL cholesterol and triglycerides, we have tested the hypothesis that mutations in the genes encoding lipoprotein lipase (LPL) or hepatic lipase (HTGL) may contribute to the formation of coronary atherosclerosis and, thus, of coronary heart disease (CHD). The entire coding and boundary regions of LPL and HTGL genes were analyzed by direct sequencing in 20 patients with both LHDL/HTG and diagnosed CHD.

Phospholipase A(2) is involved in thapsigargin-induced sodium influx in human lymphocytes.

Previously, we reported that emptying of intracellular Ca(2+) pools with endoplasmatic Ca(2+)-ATP-ase inhibitor thapsigargin leads to the Na(+) influx in human lymphocytes (M. Tepel et al., 1994, J.

Effects of testosterone suppression in young men by the gonadotropin releasing hormone antagonist cetrorelix on plasma lipids, lipolytic enzymes, lipid transfer proteins, insulin, and leptin.

We investigated in a pilot study the effect of testosterone suppression on lipoprotein metabolism, insulin, and leptin in 10 men who were treated either with cetrorelix, an antagonist of gonadotropin releasing hormone, or with placebo (P). Group C + C (n = 4) was treated with 10 mg cetrorelix as daily subcutaneous injections for five days and with a subsequent injection of 60 mg cetrorelix depot. Group C + P (n = 3) received 10 mg cetrorelix as daily intramuscular injections for five days and a subsequent injection of placebo depot.

Aberrant oxidation of the cholesterol side chain in bile acid synthesis of sterol carrier protein-2/sterol carrier protein-x knockout mice.

Peroxisomal beta-oxidation plays an important role in the metabolism of a wide range of substrates, including various fatty acids and the steroid side chain in bile acid synthesis. Two distinct thiolases have been implicated to function in peroxisomal beta-oxidation: the long known 41-kDa beta-ketothiolase identified by Hashimoto and co-workers (Hijikata, M., Ishii, N.