Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

Cholesterol Metabolite Contributes to Buildup of Atherosclerotic Plaques

By BiotechDaily International staff writers
Posted on 01 Jul 2014
A recent paper described the mechanism by which the cholesterol metabolite 27-hydroxycholesterol (27HC) contributes to the development of the fatty plaques that characterize atherosclerosis.

27HC is an abundant oxysterol metabolized by an enzyme encoded by the CYP7B1 (cytochrome P450, family 7, subfamily B, polypeptide 1) gene. This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases, which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids, and other lipids. This enzyme likely plays a minor role in total bile acid synthesis, but may also be involved in the development of atherosclerosis, neurosteroid metabolism, and sex hormone synthesis.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) used mouse and culture models to determine how 27HC modulated lipid metabolism. Results published in the June 2014 online edition of the journal Cell Metabolism revealed that in a mouse model (apoe−/−) where 27HC was elevated due to the genetically engineered deletion of CYP7B1, development of atherosclerosis was promoted without altering lipid status while estrogen-related atheroprotection was weakened.

27HC was found to upregulate proinflammatory genes and increase adhesion via the estrogen receptor in monocytes and macrophages. In endothelial cells, 27HC was also pro-adhesive via the estrogen receptor, and in contrast to estrogen, which inhibited NF-kappaB activation, 27HC stimulated NF-kappaB activation.

"When 27HC is present, estrogen's protective effects are only observed at very high levels of the hormone," said senior author Dr. Philip W. Shaul, professor of pediatrics at the University of Texas Southwestern Medical Center. "This result may explain why hormone therapy with estrogen does not provide cardiovascular benefit in women with preexisting atherosclerosis, in which 27HC is abundant in the vascular wall. Although statins have had a dramatic impact on cardiovascular health by lowering cholesterol, we still need complementary methods to combat atherosclerosis. Targeting 27HC, either by lowering the levels of this compound or by inhibiting its actions, could potentially provide a complementary approach to preventing vascular disease."

Related Links:

University of Texas Southwestern Medical Center



Channels

Drug Discovery

view channel
Image: Star-like glial cells in red surround alpha-beta plaques in the cortex of a mouse with a model of Alzheimer\'s disease (Photo courtesy of Strittmatter laboratory/Yale University).

Experimental Cancer Drug Reverses Symptoms in Mouse Model of Alzheimer's Disease

An experimental, but clinically disappointing drug for treatment of cancer has been found to be extremely effective in reversing the symptoms of Alzheimer's disease (AD) in a mouse model.... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

NanoString and MD Anderson Collaborate on Development of Novel Multi-Omic Expression Profiling Assays for Cancer

The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and NanoString Technologies, Inc. (Seattle, WA, USA) will partner on development of a revolutionary new type of assay—simultaneously profiling gene and protein expression, initially aiming to discover and validate biomarker signatures for immuno-oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.