Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Cholesterol Metabolite Contributes to Buildup of Atherosclerotic Plaques

By BiotechDaily International staff writers
Posted on 01 Jul 2014
Print article
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



Print article

Channels

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Lab Technologies

view channel
Image: A 3D nanofiber net formed by the supergelators to trap oil molecules (Photo courtesy of IBN at A*STAR / Institute of Bioengineering and Nanotechnology).

Effective Cleanup with Smart Material That Forms Oil-Trapping Net

Researchers have developed supergelators – an organic oil-scavenging material that rapidly forms a 3D net to trap oil molecules, gelatinizing into solidified masses that can be more easily removed from... Read more

Business

view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.