Innovative pharmaceutical interventions in cardiovascular disease: Focusing on the contribution of non-HDL-C/LDL-C-lowering versus HDL-C-raisingA systematic review and meta-analysis of relevant preclinical studies and clinical trials

Non-HDL-cholesterol is well recognised as a primary causal risk factor in cardiovascular disease. However, despite consistent epidemiological evidence for an inverse association between HDL-C and coronary heart disease, clinical trials aimed at raising HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their primary goals. This...

Plasma plasminogen activator inhibitor-1 level is not regulated by the hepatic low-density lipoprotein receptor-related protein [2]

Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation

Sclerostin is an osteocyte-derived negative regulator of bone formation. It inhibits BMP-stimulated bone formation both in vitro and in vivo but has no direct effect on BMP signaling. Instead, sclerostin inhibits Wnt signaling that is required for BMP-stimulated osteoblastic differentiation. Introduction: Sclerostin is a member of the Dan family...

Cholesteryl ester transfer protein inhibition: Effect on reverse cholesterol transport?

Chemicals / CAS: 2 methylpropanethioic acid s [2 [1 (2 ethylbutyl)cyclohexylcarboxamido]phenyl] ester, 211513-37-0; atorvastatin, 134523-00-5, 134523-03-8; nicotinic acid, 54-86-4, 59-67-6; torcetrapib, 262352-17-0; Carrier Proteins; CETP protein, human; Cholesterol Ester Transfer Proteins; Cholesterol Esters; Cholesterol, HDL; Glycoproteins;...

Quantitative structure activity relationship studies on the flavonoid mediated inhibition of multidrug resistance proteins 1 and 2

In the present study, the effects of a large series of flavonoids on multidrug resistance proteins (MRPs) were studied in MRP1 and MRP2 transfected MDCKII cells. The results were used to define the structural requirements of flavonoids necessary for potent inhibition of MRP1- and MRP2-mediated calcein transport in a cellular model. Several of...

Effect of homocysteine-lowering nutrients on blood lipids: Results from four randomised, placebo-controlled studies in healthy humans

Background: Betaine (trimethylglycine) lowers plasma homocysteine, a possible risk factor for cardiovascular disease. However, studies in renal patients and in obese individuals who are on a weight-loss diet suggest that betaine supplementation raises blood cholesterol; data in healthy individuals are lacking. Such an effect on cholesterol would...

Interplay between MRP Inhibition and Metabolism of MRP Inhibitors: The Case of Curcumin

The multidrug resistance proteins MRP1 and MRP2 are efflux transporters with broad substrate specificity, including glutathione, glucuronide, and sulfate conjugates. In the present study, the interaction of the dietary polyphenol curcumin with MRP1 and MRP2 and the interplay between curcumin-dependent MRP inhibition and its glutathione-dependent...