Amyloid-β (Aβ), major constituent of senile plaques in Alzheimer's disease (AD), is generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Several lipids, especially cholesterol, are associated with AD. Phytosterols are naturally occurring cholesterol plant equivalents, recently been shown to cross the blood–brain-barrier accumulating in brain. Here, we investigated the effect of the most nutritional prevalent phytosterols and cholesterol on APP processing. In general, phytosterols are less amyloidogenic than cholesterol. However, only one phytosterol, stigmasterol, reduced Aβ generation by (1) directly decreasing β-secretase activity, (2) reducing expression of all γ-secretase components, (3) reducing cholesterol and presenilin distribution in lipid rafts implicated in amyloidogenic APP cleavage, and by (4) decreasing BACE1 internalization to endosomal compartments, involved in APP β-secretase cleavage. Mice fed with stigmasterol-enriched diets confirmed protective effectsin vivo, suggesting that dietary intake of phytosterol blends mainly containing stigmasterol might be beneficial in preventing AD.

Tim Vanmierlo, Oliver Weingärtner, Susanne van der Pol, Constanze Husche, Anja Kerksiek, Silvia Friedrichs, Eric Sijbrands, Harry Steinbusch, Marcus Grimm, Tobias Hartmann, Ulrich Laufs, Michael Böhm, Helga E. de Vries, Monique Mulder, Dieter Lütjohann

Hypercholesterolaemia is a risk factor of cardiovascular diseases and is therefore a major target for primary and secondary prevention.^1,2 Maintaining a healthy diet and lifestyle reduces cardiovascular risk.³ ‘Functional foods’ supplemented with phytosterols are advertised for the management of hypercholesterolaemia and have become a widely used non-prescription approach to lower plasma cholesterol levels. It is estimated that in 2005 worldwide 3 billion US-dollars were spent on various functional foods that have regulator-approved health claims for the management of elevated cholesterol levels.⁴

PURPOSE: To determine the hemodynamic significance of arteriographically detected renal arterial stenosis by obtaining pressure gradients with a miniaturized pressure guide wire. MATERIALS AND METHODS: Forty-six renal arterial stenoses in 38 patients were assessed in terms of severity and then subjected to gradient determination before and after angioplasty. The patients (mean age, 63 years) had a mean serum creatinine value of 1.3 mg/dL ± 0.4 (114.9 μmol/L ± 35.4 [SD]) and required on average three medications for blood pressure control. The mean degree of stenosis diameter was 51% ± 17 (range, 12%–85%). RESULTS: The systolic and mean arterial pressure gradients with and those without vasodilatation were highly correlated with stenosis severity, systolic blood pressure, and serum creatinine as a curvilinear fit (r = 0.9, P < .01). At 50% stenosis severity, the mean pressure gradient was 22 mm Hg. CONCLUSION: Patients with a pressure gradient greater than 20 mm Hg should be good candidates for renal arter...

Low-density lipoproteins (LDL) are atherogenic and represent a strong cardiovascular risk factor. Therefore, LDL-cholesterol (LDL-C) remains the primary target in lipid lowering therapy. However, since many cardiovascular events occur despite an optimal LDL-C, it is necessary to focus on the remaining cardiovascular risk. Treatment of low high-density lipoprotein-cholesterol (HDL-C) and high triglycerides (TG) are options to achieve cardiovascular risk reduction beyond LDL. HDL mediates reverse cholesterol transport and exerts several other athero-protective effects. Epidemiologic evidence has shown that low HDL-cholesterol (HDL-C) is a strong and independent cardiovascular risk marker. However, since the anti-atherogenic effects of HDL particles rather depend on their functionality rather than on their cholesterol content, an increase in HDL-C concentration does not always have to result in a clinical benefit. Besides established strategies to increase HDL-C, e.g. with fibrates and nicotinic acid, CETP (Cholesteryl ester transfer protein)-inhibition is a promising new therapeutic option. The failure of torcetrapib, the first CETP-inhibitor, seems to be attributed to "off-target" effects. Treatment with the newer CETP-inhibitors dalcetrapib and anacetrapib has been shown to be efficacious and safe - but their usefulness in clinical practice remains to be determined in ongoing clinical endpoint trials. TG concentrations have been shown to correlate with cardiovascular risk. However, interpretation of plasma TG concentrations remains difficult due to considerable intra-individual variability of plasma concentrations. Post-prandial triglyceride concentrations may be better predictors of cardiovascular risk than fasting TG. In patients with hypertriglyceridemia, achievement of the LDL-C goal remains the primary lipid target. The basis of therapy in patients with hypertriglyceridemia are life style modifications. In addition, non-HDL-C should be addressed. For selected patients, treatment with fibrates, nicotinic acid or omega-3 fatty acids are available to lower TG concentrations. In summary, the focus of lipid therapy is the reduction of cardiovascular risk rather than the modification of lipoprotein sub-fractions. Ongoing research points towards a shift of the focus from the HDL-C concentrations to parameters of HDL function and from fasting TG to TG kinetics.