Scientists from the Indiana University School of Medicine found that the mutation that causes neurofibromatosis type 1 disease leads to arterial inflammation and damage that is similar to the long-term damage that can occur as people age. They reported their findings in the March issue of the Journal of Clinical Investigation.
Neurofibromatosis results from mutations in a gene called NF1, which causes tumors to form in the cells that make up the protective sheaths around nerves. In humans, NF1 mutations resulting in neurofibromatosis occur in one in 3,500 births, making it the most common genetic disease in humans that results in a predisposition to cancer.
However, cardiovascular disease in children with neurofibromatosis is a significant but under-recognized problem for which the patients are rarely tested, said David Ingram, M.D., associate professor of pediatrics and of biochemistry and molecular biology and principal investigator of the research team. Moreover, he said, "It's often a silent killer with no symptoms or warnings in advance of a catastrophic event – the children present with a heart attack or stroke."
A 2001 analysis of death certificates by Jan Friedman, M.D., Ph.D, of the University of British Columbia in Vancouver, found that the median age of death of NF1 patients was 15 years younger than the general population. NF1 patients who died at age 30 or younger were more than seven times as likely as normal patients to have been diagnosed with a cardiovascular problem.
Using genetic experiments in mice Dr. Ingram and his team were able to narrow the cause of the cardiovascular problems down to the inflammatory cells delivered to the site of the damaged blood vessel, ruling out potential effects from NF1 gene mutations in the blood vessel muscle cells and the cells that line the inside of the blood vessels.
In addition, they compared blood samples from a small group of human patients with and without the NF1 mutation and found that the neurofibromatosis patients had significant levels of inflammatory cells and other compounds that pose a higher risk of cardiovascular disease.
The IU researchers, in collaboration with Dr. Friedman in Vancouver, have begun a pilot clinical trial to evaluate potential diagnostic tests, including blood pressure monitoring and ultrasound tests of carotid arteries, that might enable physicians to discover and treat neurofibromatosis patients who are developing cardiovascular problems.
"We think that if we can demonstrate this association with vascular effects and the ability to diagnose them we could proceed to an intervention clinical trial. Statins have anti-inflammatory effects and there are other agents that could potentially be used," Dr. Ingram said.
The clinical trial protocols used in this research were developed with the assistance of the Indiana Clinical and Translational Sciences Institute. Funding for the research was provided by grants from the National Institutes of Health and the Department of Defense.
Dr. Ingram is a member of the Wells Center for Pediatric Research, the Indiana Center for Vascular Biology and Medicine, and the Indiana University Melvin and Bren Simon Cancer Center.
The IU School of Medicine is on the Indiana University-Purdue University Indianapolis campus.
Eric Schoch | EurekAlert!
Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
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...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
25.09.2017 | Power and Electrical Engineering
25.09.2017 | Health and Medicine
25.09.2017 | Physics and Astronomy