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!
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy