A new driver of atherosclerosis has been identified by researchers at UT Southwestern Medical Center. This molecule, known as 27HC (27-hydroxycholesterol), has been found to exacerbate the development of the condition, and may prove to be a promising therapeutic target.
Atherosclerosis is characterized by the build-up of lesions (or plaques) formed from lipids, such as cholesterol and fatty acids. Ruptured plaques can partially or completely block blood flow, potentially leading to a heart attack or stroke. A member of a larger family of molecules known as oxysterols, 27HC is produced during the normal breakdown of cholesterol and is known to accumulate in atherosclerotic plaques.
This is Dr. Shaul,UT Southwestern Medical Center.
Credit: UT Southwestern
The new study, conducted by a team of UT Southwestern researchers led by senior author Dr. Philip Shaul, sought to identify the impact of 27HC on atherosclerosis. Dr. Shaul is Vice Chair for Research and Professor of Pediatrics, and Director of the Center for Pulmonary and Vascular Biology at UT Southwestern. The study's findings – first-authored by Dr. Michihisa Umetani, Assistant Professor of Pediatrics and Pharmacology – were recently published in Cell Metabolism.
Using animal models and other strategies, the researchers found that 27HC promotes the formation of atherosclerotic plaques, causing a doubling in the accumulation of lipids in the arterial wall. 27HC achieves this buildup through mechanisms mediated by estrogen receptors, which normally enable the hormone estrogen to protect against the development and progression of atherosclerosis. By blocking estrogen receptors, 27HC prevents the beneficial effects of estrogen and promotes atherosclerosis.
"When 27HC is present, estrogen's protective effects are only observed at very high levels of the hormone," said Dr. Shaul, holder of the Associates First Capital Corporation Distinguished Chair in Pediatrics. "This result may explain why hormone therapy with estrogen does not provide cardiovascular benefit in women with pre-existing atherosclerosis, in which 27HC is abundant in the vascular wall."
Probing further into the underlying mechanisms, the researchers discovered that 27HC triggers inflammation in the arterial wall, a key step in the establishment of atherosclerotic plaques. This detrimental effect was characterized by exaggerated production of molecules that drive inflammation, called cytokines, and enhanced attachment on the arterial wall of immune cells known as macrophages. It is the recruitment of macrophages that then accumulate lipids (such as cholesterol) that triggers the formation of atherosclerotic plaques.
"Although statins have had a dramatic impact on cardiovascular health by lowering cholesterol, we still need complementary methods to combat atherosclerosis," Dr. Shaul said. "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."
Other UT Southwestern researchers involved in the study include Dr. Pritam Ghosh, Assistant Professor of Internal Medicine; Dr. Tomonori Ishikawa, postdoctoral research fellow in Pediatrics; Dr. Chieko Mineo, Associate Professor of Pediatrics; and Junko Umetani and Mohamed Ahmed, research assistants in Pediatrics.
The study was funded by support from the National Institutes of Health, the American Diabetes Association, and an unrestricted endowment provided to Dr. Shaul by the Associates First Capital Corporation.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.
Remekca Owens | Eurek Alert!
Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center
Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy