Selective Correction of Genotype Yield by Probucol in HDL-Deficient Mice Propagation.

Aim: Probucol is a controversial drug to inhibit ATP-binding cassette transporter A1 (ABCA1) and to exhibit some positive clinical effects such as regression of xanthomas. It reportedly rescues female infertility in scavenger receptor BI-deficient mice. Here, we investigated the effect of probucol on propagation in HDL-deficient mice as alternative models for impaired HDL-mediated cholesterol delivery.

A case of floating thrombus in the ascending aorta that caused recurrent peripheral arterial embolic events.

We report the case of a 62-year-old man with recurrent arterial embolisms to his arms caused by a thrombosis of the ascending aorta. He had developed a left brachial artery embolism 8 years previously, but presented with a right brachial artery embolus on this occasion. A clot-like mass was seen in the ascending aorta on computed tomography without significant atherosclerosis.

High density lipoprotein turnover is dependent on peroxisome proliferator-activated receptor α in mice.

Aim: Peroxisome proliferator-activated receptor (PPAR) α is a nuclear receptor that through sensing fatty acid metabolites as ligands regulates genes involved in lipid transport and metabolism (Atherosclerosis 205: 413, 2009). Disruption of the PPARα gene, however, may not lead to apparent changes in phenotypes, perhaps due to compensation by other members of the nuclear receptor superfamily. We characterized cholesterol homeostasis in PPARα-null mice on a C57BL/6 background with a focus on HDL metabolism.

Cholesterol homeostasis in ABCA1/LCAT double-deficient mouse.

We examined cholesterol homeostasis in mice with the two major cholesterol transport pathways for catabolism interrupted by disrupting abca1, lcat, or both. Plasma HDL markedly decreased in these genotype but LDL/VLDL decreased only in the double deficiency. Fractional catabolic rate of HDL increased in the order of wild type View Article and Find Full Text PDF

On the mechanism for PPAR agonists to enhance ABCA1 gene expression.

Expression of ATP binding cassette transporter A1 (ABCA1), a major regulator of high density lipoprotein (HDL) biogenesis, is known to be up-regulated by the transcription factor liver X receptor (LXR) alpha, and expression is further enhanced by activation of the peroxisome proliferator activated receptors (PPARs). We investigated this complex regulatory network using specific PPAR agonists: four fibrates (fenofibrate, bezafibrate, gemfibrozil and LY518674), a PPAR delta agonist (GW501516) and a PPAR gamma agonist (pioglitazone). All of these compounds increased the expression of LXRs, PPARs and ABCA1 mRNAs, and associated apoA-I-mediated lipid release in THP-1 macrophage, WI38 fibroblast and mouse fibroblast.