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Low-density lipoprotein (LDL) cholesterol (LDL-C) is a causal risk factor for cardiovascular complications. A target value is set according to risk, guideline-based and individual basis. We now have the means to lower LDL‑C levels to ranges that are even associated with plaque volume regression. Moreover, lipid treatment is an example of how pharmacotherapy has evolved from classical selective inhibition of enzymes by drugs (e.g. statins) to targeted neutralization of proteins by antibodies. The reduction of atherogenic lipoproteins by specific inhibition or reduction of mRNA of target proteins, e.g. PCSK‑9, ANGPLT3, ApoC-III or Apo (a), and possibly one day by vaccination or even CRISP-based gene therapy will in the long term lead to new concepts in the treatment and prevention of dyslipidemia and cardiovascular complications. The cumulative exposure of atherogenic lipoproteins to the vessel wall is determined by the time-averaged LDL‑C level. This essentially depends on patient adherence and prescribed treatment intensity by physicians. Therefore, it is likely that treatment adherence influences the cumulative benefit of treatment. Accordingly, the new therapeutic strategies mentioned above with presumably higher adherence rates could help to optimize cardiovascular prevention. Early and effective LDL‑C lowering could drastically reduce the incidence of cardiovascular complications in the long term and help to maintain the health of our patients.LDL(„low-density lipoprotein“)-Cholesterin (LDL-C) ist ein kausaler Risikofaktor für kardiovaskuläre Komplikationen. Ein Zielwert wird risikobezogen, leitlinienbasiert und individualisiert festgelegt. Wir haben heutzutage die Möglichkeiten, LDL-C-Werte in Bereiche zu senken, die sogar mit einer Regression des Plaquevolumens verbunden sind. Zudem ist die Lipidtherapie ein Beispiel, wie sich die Pharmakotherapie von klassischen selektiven Hemmungen von Enzymen durch Medikamente (z. B. Statine) zur gezielten Neutralisierung von Proteinen durch Antikörper entwickelt hat. Die Reduktion atherogener Lipoproteine durch spezifische Hemmung oder Verminderung der mRNA von Zielproteinen (z. B. PCSK9, ANGPLT3, ApoC-III oder Apolipoprotein[a]) sowie eventuell eines Tages durch Impfung oder auch CRISP-basierte Gentherapie wird langfristig zu neuen Konzepten in der Therapie und Prävention von Fettstoffwechselstörungen und kardiovaskulären Komplikationen führen. Die kumulative Exposition atherogener Lipoproteine für die Gefäßwand wird durch den zeitlich gemittelten LDL-C-Wert bestimmt. Dieser hängt wesentlich von der Adhärenz des Patienten und der verordneten Behandlungsintensität durch Ärzte ab. Daher ist es wahrscheinlich, dass die Therapietreue den kumulativen Nutzen der Therapie beeinflusst. Entsprechend könnten die neuen, o. a. Therapiestrategien mit vermutlich höheren Adhärenzraten dazu beitragen, die kardiovaskuläre Prävention zu optimieren. Eine frühzeitige und effektive LDL-C-Senkung könnte langfristig das Auftreten kardiovaskulärer Komplikationen drastisch reduzieren und dazu beitragen, die Gesundheit unserer Patienten zu erhalten.

Lipoprotein apheresis is an extracorporeal procedure for the treatment of patients with homozygous familial hypercholesterolemia, patients with severe treatment-resistant hypercholesterolemia and patients with lipoprotein(a) hypercholesterolemia, who show progressive atherosclerotic cardiovascular disease despite optimal treatment. This article reports on the historical developments of the procedures, the most frequently used methods for apheresis as well as the data situation on efficacy and tolerability. Randomized prospective studies on clinical outcomes are not available. Furthermore, the article reports on a patient with homozygous familial hypercholesterolemia and 34 years of treatment with heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) apheresis, the longest treatment of this kind worldwide. A second patient with combined heterozygous familial hypercholesterolemia and 31 years of liposorber and HELP apheresis is also described. The observational studies and the case reports demonstrate the safety and long-term tolerability of the procedure.Die Lipoproteinapherese ist ein extrakorporales Verfahren zur Behandlung von Patienten mit homozygoter familiärer Hypercholesterinämie (FH), Patienten mit schwerer, therapieresistenter Hypercholesterinämie und Patienten mit Lipoprotein(a)-Hypercholesterinämie und progredienter Atherosklerose unter Therapie. Wir berichten über die historischen Entwicklungen der Verfahren, die am häufigsten eingesetzten Apheresemethoden sowie die Datenlage zu Wirksamkeit und Verträglichkeit. Randomisierte, prospektive Studien mit klinischen Endpunkten liegen nicht vor. Weiterhin berichten wir über einen Patienten mit homozygoter FH und 34 Jahren Behandlung mit heparininduzierter extrakorporaler LDL(„low-density lipoprotein“)-Präzipitation(HELP)-Apherese, der weltweit längsten Behandlung dieser Art, und einem zweiten Patienten mit kombinierter heterozygoter FH und 31 Jahren Liposorber®- und HELP-Apherese. Die Fallberichte und Beobachtungsstudien demonstrieren die Langzeitverträglichkeit und die Sicherheit der Verfahren.

Metabolism and Function of High-Density Lipoproteins (HDL)

Congenital disorders of lipid metabolism are caused by a wide range of variants of the genes for receptors, apolipoproteins, enzymes, transfer factors, and cellular cholesterol transporters. Clinically most relevant are autosomal dominant familial hypercholesterolemia (FH) and familial combined hyperlipoproteinemia (FCHL). FH has a prevalence of 1:250. It is due to mutations of the low density lipoprotein (LDL) receptor, less often to mutations of the apolipoprotein B (APOB), the proprotein convertase subtilisin/kexin type 9 (PCSK9), or the signal transducing adapter family member 1 (STAP1). FH often leads to early atherosclerosis. Its diagnosis can definitely be made only by molecular genetic testing. The detection of mutations of the LDLR, APOB, or PCSK9 is an indicator for extremely high cardiovascular risk, independently of the concentration of LDL cholesterol. FCHL is also common (1:100) and is seen in about 10% of patients with early myocardial infarction. It is produced by combinations of frequent genetic variants affecting triglycerides and LDL cholesterol. Other monogenic hyperlipoproteinemias (HLP) affect the catabolism of chylomicrons (familial chylomicronemia) or of remnants of triglyceride-rich lipoproteins (type III hyperlipoproteinemia). Multiple hereditary disorders in HDL metabolism - with a broad spectrum of clinical significance - are known. Currently, second generation sequencing methods are used to simultaneously analyze multiple disease-causing genes. This approach cost-neutrally provides additional information such as the genetic risk of atherosclerosis and predisposition to statin intolerance.

The study aimed to investigate the distribution of specific immune responses (IgG) to Borrelia burgdorferi using a line immunoassay with recombinant VlsE (variable major protein-like sequence, expressed) protein and synthetic C peptide among other antigens. We compared the immune responses to VlsE protein and CA total of 1355 blood samples from dogs suspected of Borrelia infection were analysed. The line immunoassay employed nine antigens.A total of 64.4% of all samples tested negative, 16.4% were positive for an infection and 17.4% were positive for vaccination. Band patterns specific for both infection and vaccination were observed in 1.2% of the dogs. The bands that most frequently tested positive were p100 (24.3%), p31/OspA (18.5%), CTesting using a line immunoassay allows for qualitative analyses of different immune responses to various antigens used as probes. In our study, 26% of the dogs displayed discrepant results with regard to VlsE and C

Background: Current guidelines recommend measuring plasma lipids in fasting patients. Recent studies, however, suggest that variation in plasma lipid concentrations secondary to fasting time may be minimal. Objective of the present study was to investigate the impact of fasting time on plasma lipid concentrations (total cholesterol, HDL and LDL cholesterol, triglycerides). A second objective was to determine the effect of non-alcoholic fatty liver disease exerted on the above-mentioned lipid levels. Method: Subjects participating in a population-based cross-sectional study (2,445 subjects; 51.7% females) were questioned at time of phlebotomy regarding duration of pre-phlebotomy fasting. Total cholesterol, LDL and HDL cholesterol, and triglycerides were determined and correlated with length of fasting. An upper abdominal ultrasonographic examination was performed and body-mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Subjects were divided into three groups based on their reported fasting periods of 1–4 h, 4–8 h and > 8 h. After application of the exclusion criteria, a total of 1,195 subjects (52.4% females) were included in the study collective. The Kruskal-Wallis test was used for continuous variables and the chi-square test for categorical variables. The effects of age, BMI, WHR, alcohol consumption, fasting time and hepatic steatosis on the respective lipid variables were analyzed using multivariate logistic regression. Results: At multivariate analysis, fasting time was associated with elevated triglycerides (p = 0.0047 for 1–4 h and p = 0.0147 for 4–8 h among females; p, Hintergrund: Die aktuellen Leitlinien zur kardiovaskulären Risikoprädiktion empfehlen eine Messung der Plasmalipide am nüchternen Patienten, um individuelle Schwankungen der Lipidwerte zu minimieren und um einen vergleichbaren metabolischen Zustand zu erreichen. Aktuelle Studien legen jedoch eine geringe Schwankung der Lipidwerte in Abhängigkeit von der Nüchternzeit nahe. Ziel der vorliegenden Arbeit ist die Untersuchung des Einflusses der Nüchternzeit auf die Höhe des Gesamt-, HDL- (High Density Lipoprotein) und LDL- (Low Density Lipoprotein) Cholesterins, sowie der Triglyceride in einer bevölkerungsbasierten Querschnittsstudie. Des Weiteren soll untersucht werden, ob das Vorliegen einer nichtalkoholischen Fettlebererkrankung einen Einfluss auf die Höhe der genannten Lipidwerte hat. Methoden: Im Rahmen einer Bevölkerungsbasierten Querschnittsstudie (EMIL – Echinococcus Multilocularis In Leutkirch) wurden 2445 Probanden (51,7% Frauen) bezüglich ihrer Nüchternzeit bei Blutentnahme befragt. Laborchemisch wurden Gesamtcholesterin, LDL-Cholesterin, HDL-Cholesterin und Triglyceride in Abhängigkeit der Nüchternzeit gemessen. Die Probanden wurden sonographisch untersucht, BMI (Body Mass Index) und WHR (Waist to Hip Ratio) wurden bestimmt. Die Nüchternzeit wurde eingeteilt in 1-4 h, 4-8 h und > 8 h. Nach Anwendung der Ausschlusskriterien wurden 1195 Probanden (52,4% Frauen) in die Studie aufgenommen. Zur Untersuchung auf geschlechtsspezifische Unterschiede wurde für stetige Variablen der Kruskal-Wallis-Tests und für kategoriale Variablen der Chi-Square-Test angewandt. Unterschiede der Lipidwerte zwischen den einzelnen Nüchternzeitgruppen wurden mittels des Kruskal-Wallis-Tests untersucht. Mit Hilfe der multivariaten logistischen Regression wurde der Einfluss von Alter, BMI, WHR, Alkoholkonsum, Nüchternzeit und Steatosis hepatis auf die genannten Lipidparameter untersucht. Ergebnisse: Insgesamt 279 Probanden (23,4%) wiesen sonographisch eine Fettleber auf (33% Frauen). In der multivariaten Analyse war die Nüchternzeit mit erhöhten Triglyceriden bei beiden Geschlechtern (p=0,0047 für 1-4 h und p=0,0147 für 4-8 h bei Frauen, p

Einleitung: Kardiovaskuläre Erkrankungen sind die Haupttodesursache weltweit, wobei Lipidstoffwechselstörungen mit erhöhtem Cholesterin, insbesonde Low- Density Lipoprotein (LDL)-Cholesterin, und arterielle Hypertension hierfür als unabhängige Risikofaktoren gelten. In Studien konnte eine Assoziation von erhöhten Blutdruckwerten und erhöhten Cholesterin-, bzw. LDL-Levels nachgewiesen werden. Ein möglicher Mechanismus für eine Beeinflussung der Blutdruckregulation durch LDL ist die durch LDL verursachte Einschränkung der flussabhängigen Vasodilatation (FMD), die in verschiedensten Gefäßgebieten gezeigt wurde. Ziel der Arbeit ist, zu untersuchen, ob die durch LDL verursachte Einschränkung der FMD durch eine Wechselwirkung mit sympathischen Adrenorezeptoren (AR) verursacht wird. Methoden: Flussabhängiger isometrischer Gefäßtonus, intrazelluläres Membranpotential und cAMP- und cGMP- Konzentrationen wurden unter Einfluss von Kontrolllösung (Krebs-Lösung), LDL- Lösung und LDL-Lösung unter Zugabe von AR-Blockern an Koronararterienpräparaten aus Herztransplantationen von insgesamt 46 Patienten gemessen. Ergebnisse: Im Vergleich zu Krebslösung beeinflusste LDL die FMD und verursachte eine relative Kontraktion Δ(T3 - T100): Krebs 0,496 g; LDL 0,278 g). Komplette Blockade von α-(Phentolamin 10-7 mol/l) und β-Rezeptoren (Propranolol 10-7 mol/l) führte zu einer ca. 50% verminderten Reduktion der FMD durch LDL. Die Blockade von entweder α- oder β-Rezeptor führte zu jeweils kleineren Effekten, die in der Summe mit dem Effekt unter kombinierter Blockade übereinstimmten. Gleiche Effekte konnten bei Messung der Membranpotentiale der Gefäßmuskelzellen und der Konzentration der intrazellulären zyklischen Nukleotide festgestellt werden. Mit den erhobenen Messdaten konnten eine intakte chemoelektrische und chemomechanische, sowie eine lineare elektromechanische Kopplung an menschlichen Koronararterien nachgewiesen werden. Diskussion: Wir konnten zeigen, dass die von LDL verursachte Einschränkung der FMD zu 50% über eine Wechselwirkung zwischen LDL und α- wie auch β-Rezeptor bedingt ist. Die Ergebnisse zeigten sich sowohl auf mechanischer und elektrischer, als auch auf Ebene der Second Messenger. Da eine einzelne Blockade von α- und β-Rezeptor jeweils zu einer relativen Dilatation unter LDL führte, gehen wir von einer Aktivierung des α- und Inhibition des β-Rezeptors durch LDL aus. Über die Beeinflussung der FMD und seine Interaktion mit den sympathischen AR kann LDL einen Einfluss auf die Blutdruckregulation nehmen. Unterstützt wird diese Vermutung durch eine nachgewiesene Korrelation von niedrigeren LDL-Levels mit niedrigen Blutdruckwerten nach Gabe von Statinen, unabhängig von pleiotropen Statin- Effekten. Wir weisen in unserer Studie folglich nach, dass die unabhängigen Risikofaktoren Hypertonie und LDL-Cholesterin auf Ebene der sympathischen AR und der FMD verknüpft sind., Introduction: Cardiovascular diseases are the main cause of death worldwide, whereas disorders of lipid metabolism with elevated blood cholesterol, especially low-density lipoprotein(LDL)-cholesterol, and arterial hypertension count as independent risk factors. Studies show an association between elevated blood pressure and both elevated cholesterol and LDL levels, respectively. One of the underlying mechanisms for the influence of LDL on blood pressure regulation is an LDL-induced impairment of the flow-mediatated vasodilation (FMD), which has been demonstrated in different types of blood vessels. This work is aiming to examine if an interaction between LDL and sympathetic adrenoreceptors (AR) could be the underlying cause for an LDL- induced impairment of FMD. Methods: Flow-dependent isometric tension, intracellularly recorded membrane potential and intracellular cAMP- and cGMP- concentration were measured under the influence of Krebs solution (control), LDL solution and LDL solution with added AR-blockers in segments of coronary arteries from heart transplantations of 46 patients in total. Results: As compared to Krebs solution, LDL affected FMD and caused a relative contraction Δ(T3 - T100): Krebs 0,496 g; LDL 0,278 g. Complete blockade of both α- (phentolamin 10-7 mol/l) and β-receptors (propranolol 10-7 mol/l) resulted in a ∼50% reduction of LDL-induced FMD impairment. Blockage of either α- or β-receptors showed smaller effects which added up to the measured effect under blockage of both receptors. Similar effects were apparent in the recorded membrane potential of the vascular smooth muscle cells and in the intracellular concentration of the cyclic nucleotides. From our data, we could show an intact chemoelectrical, chemomechanical and furthermore a linear electromecanical coupling in human coronary arteries. Discussion: We could show that the LDL-induced impairment of FMD is in ∼50% due to an interaction between LDL and both α- and β-receptors. Similar results could be shown in mechanical and electrical measurements and on the level of second messengers. Since blockage of each receptor resulted in a relative dilatation, we assume that the LDL effect is caused by a stimulation of α- and an inhibition of β-adrenoreceptors. Through its influence on FMD and its interaction with sympathetic AR, LDL might be implicated in blood pressure regulation. This finding is supported by studies that suggest that lower LDL levels, achieved through administration of statins, are correlated with lower blood pressure, independent of pleiotropic statin effects. Therefore we demonstrate in this study that the former independend risk factors of elevated LDL-cholesterol and high blood pressure are linked on the level of sympathetic AR and through FMD.

It is still a much debated question whether antidiabetic therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with advanced type 2 diabetes. New findings result from ACCORD, ADVANCE and VADT. These trials reveal that microvascular and macrovascular effects of intensive glucose lowering have to be considered separately: Glycemic control convincingly demonstrated to have a protective impact on microvascular complications, especially nephropathy. However, macrovascular benefits remain doubtful in these megatrials and have to be considered in connection with the individual global risk. On the other hand, the Diabetes Intervention Study (DIS) and UKPDS 10-year follow-up results yielded better cardiovascular outcomes for those patients who received intensive glucose-lowering therapy very early after diabetes diagnosis, but the favourable influences did not manifest until a time period of 1 - 2 decades. For the first time, the cardiovascular benefit of an antidiabetic substance (pioglitazone) could be verified in the large-scale outcome-trial PROactive for patients with advanced diabetes and multiple manifestations of macroangiopathy. The results provide strong support for a beneficial influence on macrovascular complications just under 3 years of treatment. Nevertheless, the positive findings did not result from better glycemic control, but from the complexity of effects of PPARgamma agonist pioglitazone on insulin resistance, lipoprotein spectrum, blood pressure, endothelial function and biomarkers of subclinical inflammation. It is obvious that we need to integrate such pleiotropic effects on metabolic syndrome and cardiovascular disease to improve the quality of drug-therapy decisions. This, in turn, requires a growing body of evidence from large, long-term outcome trials - but appropriate data are still unavailable for the vast majority of antidiabetic drugs.

Chylomikronen sind Lipoproteine die durch eine geringe Dichte, große Partikeldurchmesser und einen hohen Triglycerid-Anteil charakterisiert sind. Ihre Hauptfunktion ist der Transport von Nahrungslipiden über die Lymph- und Blutbahn zu verschiedenen Geweben. Ob eine Aufnahme von Chylomikronen durch T-Zellen erfolgt und die T-Zellfunktion beeinflusst, wurde bisher wenig untersucht. In dieser Arbeit wurde eine Methode entwickelt, die eine Beobachtung der Endozytose von Chylomikronen durch Leukozyten ermöglicht. Die Isolierung der Chylomikronen aus Plasma erfolgte durch mehrere Zentrifugations- und Waschschritte. Durch Elektrophorese sowie durch Western-Blot Analyse mit Apolipoprotein B-48-Antikörpern wurden Chylomikronen in der Endpräparation nachgewiesen. Diese wurden mit Fluorescein-Isothiocyanat (FITC) konjugiert. Gebundenes FITC konnte durch Western-Blot-Analyse mit einem anti-FITC-Antikörper nachgewiesen werden. Für die Endozytoseversuche wurden zwei T-Zellrezeptor-positive Zelllinien (MOLT 14 und MOLT 16) und eine Makrophagenzelllinie (Mono-Mac-6) verwendet. Nach Inkubation mit FITC-markierten Chylomikronen wurde bei allen drei Zelllinien eine Fluoreszenz der Zellen durchflusszytometrisch nachgewiesen. Durch konfokale Mikroskopie wurden zytoplasmatische, teilweise granuläre fluoreszierende Strukturen beobachtet. Die Ergebnisse der Arbeit bestätigen die spezifische Aufnahme von Chylomikronen durch Zellen des Immunsystems. Chylomicrones are one main group of lipoproteins characterized by low density, enormous particle diameter and a high portion of triacylglycerid. Chylomicrones are formed in the intestinal mucosa. Their main function is to transport alimentary lipids via the lymph- and bloodstream to various tissues. Whether chylomicrones are absorbed by cells of the immune system and what importance such a process has for the function of the immune system has not yet been tested extensively. For the presented paper a method to monitor the endocytosis of chylomicrones was developed. Multiple zentrifugation- and washing-steps were used to isolate the chylomicrones from human plasma. Conjugation with fluorescein-isothiocyanat (FITC) accomplishes a labelling of chylomicrones with fluorescence. Electrophoreses under natural conditions in an agarose-matrix as well as detection of the specific apolipoprotein B-48 in a western-blot were applied in order to confirm the identity of chylomicrones. FITC attached to apolipoproteins was detected by means of western-blot-analysis with anti-FITC-antibody. In processing the endocytosis-experiments three cell lines were made use of: A macrophage cell line (Mono-Mac-6), a α/β-T-cell receptor positive (MOLT 16) and a γ/δ-T-cell receptor positive cell line. After incubation with FITC-marked chylomicrones flow cytometry verified fluorescence in all three cell lines. Convocal microscopy even made visible zytoplasmatic, in parts granular fluorescencing structures. Endozytosised chylomicrones though could not be verified by electron microscopy.

Lipopolysaccharide (LPS) is the major immunostimulatory component of Gramnegative bacteria, but its counterpart in Gram-positive bacteria is still under discussion. Looking on the Gram-positive cell wall, three components are considered to be recognised by cells of the human innate immune system: Peptidoglycan (PGN), quantitatively the main component, lipoteichoic acid (LTA) as a similar amphiphile structure compared to LPS and lipoproteins (LP). To find out more about the immunostimulatory capacity of these membrane components, the first approach in this thesis was to screen public available literature for evidence, that cytokine release in humans is connected with one or more of the named components. This research was done systematically as a meta-analysis with the four well-known Koch-Dale (K/D) criteria with a restriction to human studies. Taken together, the results of the meta-analysis indicated that PGN and LPs might play a role in cytokine induction and therefore in immune recognition of Gram-positive bacteria in humans, but the evidence for LTA being the major immune stimulus in Gram-positive bacteria is strong as it is the only investigated molecule fulfilling all K/D criteria. The interesting findings of this meta-analysis needed to be investigated experimentally. The model organism for these investigations was Staphylococcus aureus (SA), which is a frequent human pathogen and often colonises humans asymptomatically, but is also able to induce severe infections in tissue or even spreading into the blood. In the second part of the thesis, three different SA 113 mutants, which were lacking lipoproteins (Δlgt) or wall teichoic acids (ΔTA) or possessed a reduced alanine content of the LTA (Δdlt) were compared to its corresponding wildtype with respect to their immunostimulatory capacity in human primary cells. We could finally show that the different mutants differ only marginally in their immunostilumatory capacity. Despite the strong evidence that LTA is a major immunostimulatory principle of Gram-positive bacteria, recent reports suggested that not LTA but lipoproteins are the dominant immunostimulatory structures of SA. Therefore we compared the LTA from SA 113 Δlgt and its corresponding wildtype in more detail. This study clearly shows major similarities between wt and lgt LTA, but differences in immunrecognition to synthetic lipoproteins. In summary, the results of this thesis contribute to the understanding of the innate immune response with the focus on cell wall components of Gram-positive bacteria. This may lead to new approaches to treatments against Gram-positive bacterial infections in the future.

The intake of anabolic-androgenic steroids (AAS) leads to an increase in skeletal muscle mass and is prohibited as a doping measure in sport. AAS abuse is not limited to competitive athletes. It is also prevalent in subjects who do body building or resistance training for cosmetic reasons only. Out of the numerous and partly serious side effects, the cardiovascular ones are presented here. An increase in left ventricular muscle mass is well documented, and some researchers have even reported concentric hypertrophy. By contrast, resistance training without AAS intake does not lead to increased ventricular wall thickness. AAS do not affect the systolic function of the left ventricle, whereas diastolic function might be impaired. Different ultrastructural myocardial alterations have been documented in animal studies. In addition, AAS can induce arterial hypertension. Blood clotting and fibrinolysis are negatively affected, and several case studies of thrombi exist in young strength athletes. Changes in the concentration of blood lipoproteins, particularly a reduction in vessel-protective HDL cholesterol, can lead to early atherosclerosis. Many case reports exist about cardiac deaths in seemingly healthy subjects-most often body builders and other strength athletes. In fatal and nonfatal myocardial infarctions patent coronary arteries were proven frequently. Besides the prothrombotic effects of AAS, an impaired endothelial function and vasospasms are discussed hypothetically as pathomechanisms. Also, cardiomyopathies can occur due to AAS abuse. On the basis of the described possible cardiovascular side effects, it can be concluded that in cases of sudden cardiac deaths in young athletes, a misuse of AS should be excluded.

The term "coronary ectasia" describes the dilatation of one or more coronary artery segments with the signs of an impaired coronary blood flow. The prevalence, clinical significance and necessity of treatment of such a lesion is unclear.Diagnostic coronary angiographies of 7101 patients (2131 women and 4970 men) were retrospectively evaluated for the presence of dilated coronary segments. Prevalence, age- and gender distribution, cardiovascular risk factors, clinical symptoms, CRP-concentrations, prevalence of myocardial infarction as well as the coronary morphology of patients with coronary ectasia were studied. The occurrence of myocardial infarction in this group was compared to that in a control group consisting of patients with stenotic coronary artery disease.The prevalence of coronary ecstasy was 1.4 % (women: 0.56 %; men: 1.79 %), mean age of patients was 63.5 +/- 10.5 years. The right coronary artery was most frequently involved (RCA: 97 %, LAD: 30 %, RCX: 23 %, LCA: 35 %). In patients with one-vessel disease the right coronary artery was exclusively affected. In 85.1 % the dilatation of coronary segments was associated with stenotic coronary artery disease. 73.3 % of the patients with coronary ectasias suffered from angina, 33.7 % CCS (Canadian Cardiovascular Society) class III and IV. Angina in patients with coronary ecstasy did not differ from that of patients with stenotic coronary artery disease only. Patients with coronary ectasias had a higher incidence of myocardial infarction than patients with stenotic coronary heart disease (p0.001).Coronary ectasia is a relatively rare entity and often associated with stenosis. Angina is a common symptom. Patients with coronary ectasias seem to suffer more frequently from myocardial infarctions than patients with only stenotic coronary heart disease.

Atherosclerosis and coronary artery disease (CAD) are the main causes of death in the Western world, for both men and women. However, in premenopausal women CAD is less frequent than in men, but in elderly women (e.g.,75 years) myocardial infarction (MI) occurs even more often than in men. In summary, women suffer from CAD and MI but at a later age than men. Therefore it is important to observe and compare the cardiovascular risk factors in women and men. The typical CAD risk factors such as hyperlipidemia, smoking, arterial hypertension, diabetes mellitus, obesity, physical inactivity, and unhealthy nutrition are increasingly important for both genders. Many of these factors are comparable between men and women, but due to hormonal influences especially the lipoprotein metabolism shows some striking differences between men and women, but interestingly enough also between pre- and postmenopausal women. Therefore this paper will focus especially on the gender-specific differences in lipid metabolism as a potential target which might explain both the gender-specific and also pre- and postmenopausal differences in the occurrence of CAD.

Due to the manifold functions of tissue factor (TF), also tissue factor pathway inhibitor (TFPI), its endogenous antagonist, is of interest. For the determination of TFPI, either its antigen concentration or its activity can be measured.A chromogenic assay for the functional determination of TFPI is presented and modified for its application in the routine laboratory. Its suitability for daily use was evaluated by testing more than 7000 plasma samples from a heparin study in healthy volunteers. In addition, our data confirm that the method records the activity of both free- and lipoprotein-associated TFPI.The chromogenic assay proved to be rapid and easy to perform and features a high reproducibility. Due to excellent correlation of the results with the total TFPI antigen concentrations, the method represents a more rapid and economic alternative to the determination of total TFPI antigen by ELISA in plasma samples after heparin application.

An imbalance between formation and detoxification of oxygen radicals leads to oxidant stress that may increase in more intense oxidative metabolism caused by a high intake of metabolizable energy to provide metabolic intermediates for the milk synthesis and secretion. This hypothesis was tested using dairy cows and the concentration of hydroperoxides in lipids (LHP) extracted from circulative lipoprotein particles of low and very low density (LDL and VLDL/chylomicrons) as oxidant stress indicator. The particles were prepared by ultracentrifugation of serum obtained by coccygeal bleeding (13 cows, 1. parity, n=8 and 2. parity, n=5, lactation stage, 53 +/- 1.4 days post partum) and purified by precipitation. Concentrations of LHP-LDL/mg Lipoprotein correlated significantly with daily milk yield (r = 0.73, P = 0.004) or daily milk energy output (r = 0.77, P = 0.003) in contrast to LHP of VLDL/chylomicron particles. Thus, some evidence was obtained for an almost linear, positive relationship between milk productivity and oxidant stress occurring in LDL.

ZIEL: In einem Biosensormodell (PCT/EP 97/05212) wurde das Wechselspiel zwischen wassrigem Knoblauchextrakt (0,2–5,0 g/l aus LI-111-Pulver) und verschiedenen Lipoproteinen auf die arteriosklerotische Nanoplaquebildung getestet, um zu prufen, ob Knoblauch als moglicher Kandidat gegen Arterio-/Atherosklerose gelten kann. METHODIK: Die Experimente wurden mit ellipsometrischer Messtechnik durchgefuhrt, indem der adsorbierte Betrag (Nanoplaquebildung) und die Schichtdicke (Nanoplaquegrose) quantifiziert wurden. Eine ausfuhrliche Beschreibung des experimentellen Designs erfolgte in fruheren Publikationen. ERGEBNISSE: Die Adsorption von Proteoheparansulfat an eine hydrophobe Silikatoberflache zeigte einen monoexponentiellen Verlauf und war nach etwa 30 min konstant. Bereits in normaler Blut-Ca2+-Konzentration bildeten sich bei Zugabe der LDL-Plasmafraktion (100 mg/dl) eines gesunden Probanden arteriosklerotische Nanoplaques, wobei diese mit hoheren Ca2+-Konzentrationen stark zunahmen. Knoblauchextrakt, vorzugsweise in einer Konzentration von 1 g/l, verlangsamte bei akuter Applikation diesen Prozess der ternaren Nanoplaquekomplexierung deutlich bei allen verwendeten Ca2+-Konzentrationen. Bei normaler Blut-Ca2+-Konzentration von 2,52 mmol/l betrug die Knoblauch-induzierte Verminderung der Neubildung von Nanoplaques und ihrer molekularen Grose 14,8 % bzw. 3,9 % gegenuber den Kontrollen. Nach der ternaren Komplexbildung war Knoblauchextrakt, ahnlich wie HDL, in der Lage, die Nanoplaquebildung und -grose wieder zu reduzieren. Die Inkubationszeit fur HDL und Knoblauch betrug in diesen Experimenten nur jeweils 30 min. Dennoch nahm nach dieser kurzen Zeit die Ablagerung des ternaren Komplexes um 6,2 % bzw. 16,5 % ab, d. h., die komplexierten Aggregate waren prinzipiell wieder auflosbar. SCHLUSSFOLGERUNG: Durch diese Experimente konnte bewiesen werden, dass Knoblauchextrakt die Ca2+-Bindung an Proteoheparansulfat stark hemmt. In der Folge wird die Bildung des ternaren HS-PG/LDL/Ca2+-Komplexes, der anfanglich fur die Zusammensetzung der Nanoplaques und letztlich der arteriosklerotischen Plaqueentstehung verantwortlich ist, entscheidend eingeschrankt.

Lipoprotein lipase (LPL) is the central enzyme in plasma triglyceride hydrolysis. Various genetically modified mouse lines expressing either native or mutated LPL have been established, and the function of LPL in the metabolism and during lipoprotein transport has been characterized. Some of these animals showed an LPL-mediated myopathy or cardiomyopathy. Comparing the histological changes with metabolic data provides new insights in the function of LPL in metabolism and for atherogenesis.Histological and electron microscopy specimens of muscle and heart from different LPL transgenic mouse lines have been evaluated and compared to metabolic data.Presence of LPL causes a myopathy and cardiomyopathy primarily by augmenting nonenzymatic selective cholesterol ester uptake. LPL-mediated fatty acid and lipoprotein uptake is not sufficient to harm muscle tissue.It is suggested, that LPL derived from endothelial cells and macrophages--besides other atherogenic mechanisms--can mediate cholesterol ester influx into the vessel wall and thereby promote proatherogenic modifications. Although due to its hydrolytic function, LPL is generally considered an antiatherogenic enzyme, endothelial LPL can locally facilitate atherogenesis.