The arachidonic acid metabolome serves as a conserved regulator of cholesterol metabolism.

Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood.

Inhibition of hepatic scavenger receptor-class B type I by RNA interference decreases atherosclerosis in rabbits.

Objective: Scavenger receptor-class B type I (SR-BI), the receptor for HDL-cholesterol, plays a key role in HDL metabolism, whole body cholesterol homeostasis, and reverse cholesterol transport. We investigated the in vivo impact of hepatic SR-BI inhibition on lipoprotein metabolism and the development of atherosclerosis employing RNA interference.

Methods: Small hairpin RNA plasmid specific for rabbit SR-BI was complexed with galactosylated poly-l-lysine, allowing an organ-selective, receptor-mediated gene transfer.

Leoligin, the major lignan from Edelweiss, activates cholesteryl ester transfer protein.

Objective: Cholesteryl ester transfer protein (CETP) plays a central role in the metabolism of high-density lipoprotein particles. Therefore, we searched for new drugs that bind to CETP and modulate its activity.

Methods: A preliminary pharmacophore-based parallel screening approach indicated that leoligin, a major lignan of Edelweiss (Leontopodium alpinum Cass.

A murine model of phosphate nephropathy.

We established a murine model of phosphate nephropathy with secondary hyperparathyroidism. db/db mice, which develop obesity and type 2 diabetes mellitus, were uninephrectomized at the age of 6 weeks and were fed either standard chow or a phosphorus-rich diet during the next 8 weeks. Thereafter, renal cryosections showed abundant tubular casts with a strong histochemical von Kossa reaction in all db/db mice on the phosphorus-rich diet but none in the controls.

Cholesteryl ester transfer protein and hepatic lipase gene polymorphisms: effects on hepatic mRNA levels, plasma lipids and carotid atherosclerosis.

Objective: HDL modifying effects of cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) depend in part on each other. We studied associations of CETP-Taq1B and -514C>T-LIPC polymorphisms with hepatic mRNA levels, and their combined effects on plasma lipids and carotid atherosclerosis.

Methods: We genotyped the CETP-Taq1B and the -514C>T-LIPC polymorphisms in 67 obese women in whom hepatic CETP and LIPC transcript levels were determined as well as in 1549 participants of the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR).

Effect of weight loss on serum pigment epithelium-derived factor levels.

Background: Cumulating evidence suggests that the broadly acting neurotrophic pigment epithelium-derived factor is associated with visceral adiposity, the metabolic syndrome, diabetes and exerts beneficial effects on atherosclerosis. To further elucidate the relationship between pigment epithelium-derived factor and metabolic perturbations characteristic of obesity, we examined the effect of pronounced weight loss on serum levels of pigment epithelium-derived factor.

Materials And Methods: Thirty-six severely obese adults were examined before and 18 months after bariatric surgery.

[LDL-cholesterol in secondary prevention: goal-attainment in patients on lipid-lowering drugs in private practice and in hospitals in Austria (ZIEL)].

Background: A hospital-based screening project (HSP) in Austria found 47% of high-risk patients (LDL-C < 100 mg/dl) and 24% of very high-risk patients (LDL-C < 70 mg/dl) at goal. Separate data for the sexes were not reported. We analyze whether LDL-C goal attainment in patients with manifest atherosclerosis and/or diabetes on stable lipid-lowering treatment differs between private practice and hospital and between men and women.

Differential effects of NO inhibition in renal epithelial and endothelial cells in mono-culture vs. co-culture conditions.

Nitric oxide (NO) plays a critical role in the regulation of renal hemodynamics and tubular function after post-ischemic damage or sepsis. Diminished NO bioavailability contributes to endothelial dysfunction and may be caused by reduced NO synthesis due to substrate or co-factor deficiency. The aim of this study was to investigate the effects of NOS inhibition and NO depletion in a renal endo-epithelial bilayer model compared to monolayers of proximal tubular epithelial (HK-2) cells and endothelial cells of venous origin (EA.

The neuropeptide catestatin acts as a novel angiogenic cytokine via a basic fibroblast growth factor-dependent mechanism.

Rationale: The neuropeptide catestatin is an endogenous nicotinic cholinergic antagonist that acts as a pleiotropic hormone.

Objective: Catestatin shares several functions with angiogenic factors. We therefore reasoned that catestatin induces growth of new blood vessels.

Cholesteryl ester transfer protein in patients with coronary heart disease.

Background: The impact of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is a matter for ongoing debate. In this study, we analyse associations of CETP with cardiovascular endpoints in a cohort of patients with stable coronary artery disease (CAD).

Design: KAROLA is a prospective observational study of patients with CAD and a median follow-up of 8 years (n = 1132).

The liver-selective thyromimetic T-0681 influences reverse cholesterol transport and atherosclerosis development in mice.

Background: Liver-selective thyromimetics have been reported to efficiently reduce plasma cholesterol through the hepatic induction of both, the low-density lipoprotein receptor (LDLr) and the high-density lipoprotein (HDL) receptor; the scavenger receptor class B type I (SR-BI). Here, we investigated the effect of the thyromimetic T-0681 on reverse cholesterol transport (RCT) and atherosclerosis, and studied the underlying mechanisms using different mouse models, including mice lacking LDLr, SR-BI, and apoE, as well as CETP transgenic mice.

Methodology/principal Findings: T-0681 treatment promoted bile acid production and biliary sterol secretion consistently in the majority of the studied mouse models, which was associated with a marked reduction of plasma cholesterol.

Cholesteryl ester transfer protein and mortality in patients undergoing coronary angiography: the Ludwigshafen Risk and Cardiovascular Health study.

Background: The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still open to debate. In the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial, inhibition of CETP in patients with high cardiovascular risk was associated with increased high-density lipoprotein levels but increased risk of cardiovascular morbidity and mortality. In this report, we present a prospective observational study of patients referred to coronary angiography in which CETP was examined in relation to morbidity and mortality.

Atorvastatin attenuates murine anti-glomerular basement membrane glomerulonephritis.

Statins mediate many of their protective effects by lowering lipids as well as by modulating inflammation. Here, we studied their potential immunomodulatory role in renal inflammation using an autoimmune mouse model of anti-glomerular basement membrane glomerulonephritis. Oral treatment with Atorvastatin dramatically reduced albuminuria and histological changes in the kidneys as compared to vehicle-treated control animals.

Effects of weight loss on lipid transfer proteins in morbidly obese women.

Obesity is associated with lipid abnormalities leading to an increased morbidity and mortality from atherosclerotic disease. Lipid transfer proteins such as Cholesteryl Ester Transfer Protein (CETP) and Phospholipid Transfer Protein (PLTP), and lipases such as lipoprotein lipase (LPL) and hepatic lipase (HL) are involved in the pathogenesis of the obesity associated proatherogenic dyslipidemia. Nineteen severely obese female subjects undergoing laparosopic gastric banding participated in this prospective study.

The resurgence of thyromimetics as lipid-modifying agents.

The aggressive reduction of LDL-cholesterol levels by treatment with statins is a key component of preventive cardiovascular care; however, additional therapies to prevent atherosclerosis and the associated clinical sequelae are still needed. Thyromimetic compounds selective for the liver or for the thyroid hormone receptor isoform beta1 constitute a novel approach for the treatment of dyslipidemia. In preclinical studies, selective thyromimetics significantly reduced plasma cholesterol levels and provided protection from atherosclerosis by upregulating the hepatic LDL receptor and promoting reverse cholesterol transport.

Adipocyte fatty acid binding protein during refeeding of female patients with anorexia nervosa.

Background: Adipocyte fatty acid binding protein (A-FABP) has been suggested to play an important role in fat metabolism linking obesity and the metabolic syndrome. Increasing A-FABP plasma levels were observed during greatest weight loss after bariatric surgery suggesting that A-FABP may indicate changes in fat mass in dynamic situations.

Aim Of The Study: As there are no data on weight gain, we investigated the effect of refeeding anorexic patients on body composition and A-FABP plasma levels.

Influence of visceral obesity and liver fat on vascular structure and function in obese subjects.

Endothelial dysfunction and increased intima-media thickness (IMT) have been found in obese patients. Both regional fat distribution and liver steatosis may influence these markers of subclinical atherosclerosis. We sought to determine the interrelationships of endothelial function, carotid IMT, visceral and subcutaneous adipose tissue accumulation, and liver steatosis in severely obese subjects.

Influence of aspirin on SR-BI expression in human carotid plaques.

Background: We recently showed that aspirin promotes scavenger receptor class-B type I (SR-BI) protein expression in vitro in primary human macrophages and in vivo in resident peritoneal macrophages of mice.

Methods: We compared SR-BI and CD68 expression in carotid atherosclerotic specimens from endarterectomized patients with (n=38) or without (n=19) low-dose aspirin medication (100 mg/day) prior to endarterectomy.

Results: We found no differences concerning expression of CD68, indicating that aspirin did not influence macrophage content within atherosclerotic plaques.

The thyromimetic T-0681 protects from atherosclerosis.

This report describes studies in hyperlipidemic New Zealand White (NZW) rabbits investigating the impact of the liver-selective thyromimetic T-0681 on lipoprotein metabolism and the development of atherosclerosis. Prolonged treatment with T-0681 increased the hepatic expression of both LDL receptor and scavenger receptor class B, type I without affecting cholesteryl ester transfer protein activity. Upregulation of hepatic lipoprotein receptors was accompanied by a marked decrease of apolipoprotein B-containing lipoproteins, reflected by a 60% reduction of plasma cholesterol and a >70% reduction of plasma triglyceride levels.