Gene linked to inflammation in the aorta may contribute to abdominal aortic aneurysm
A gene known to be involved in cancer and cardiovascular development may be the cause of inflammation in the most common form of aortic aneurysm and may be a key to treatment, according to research from Nationwide Children's Hospital. The study, appearing online in Arteriosclerosis, Thrombosis, and Vascular Biology on October 18, 2012, is the first to show that Notch 1 signaling is activated in abdominal aortic aneurysmal tissue in mice and humans.
The aorta is the largest blood vessel in the body. Abdominal aortic aneurysm (AAA) occurs when the weakened aortic wall dilates in the abdominal portion of the vessel; they are the most common form of aortic aneurysms. AAA is a leading cause of death in the United States, especially among men over the age 65, and the disease is linked to smoking, high blood pressure and high cholesterol. AAA is extremely rare in children, but can occur in those who experience a blunt trauma or who have connective tissue diseases. Surgery is currently the only treatment for AAA and less than 20 percent of patients will survive a ruptured aneurysm.
"There is critical need to develop pharmacologic interventions that can selectively target one or more features of AAA to prevent the progression or stimulate regression in already diagnosed patients," says the study's senior author, Vidu Garg, MD a cardiologist in The Heart Center at Nationwide Children's Hospital and a principal investigator in the Center for Cardiovascular and Pulmonary Research.
Inflammation is a hallmark of AAA. The Notch 1 gene is involved in many developmental processes in humans and studies have shown its signaling pathway to be active in several inflammatory diseases.
"Notch 1 signaling is a significant regulator of the inflammatory response," says the study's lead author, Chetan Hans, PhD, principal investigator in the Center for Cardiovascular and Pulmonary Research at Nationwide Children's Hospital. "However, its role in AAA is unknown."
To examine the role of Notch 1 signaling in AAA development, Dr. Hans and colleagues first inspected tissue specimens from the abdominal aorta of patients undergoing AAA repair and a mouse model of the disease. They provide the first evidence that Notch 1 signaling is activated in these models and in human patients. They then closely examined the role Notch 1 signaling plays in the Angiotensin II-induced mouse model of AAA, when Notch 1 signaling is inhibited.
Findings showed that mice that had a genetic deficiency of Notch1 or received a chemical Notch inhibitor had less inflammation in the aorta and had a reduced incidence of AAA.
"Our data suggest that Notch 1 is an important player in the inflammatory process in the setting of AAA," says Dr. Hans. "Treatment with Notch 1-specific inhibitors may be a potentially promising strategy for slowing aneurysm development."
Dr. Hans says further studies are needed to understand the specific role of these inflammatory factors in AAA.
Provided by Nationwide Children's Hospital
- Gene discovered as cause of fatal condition Nov 03, 2011 | not rated yet | 0
- Discovery points way for new treatment for aneurysms Jan 27, 2010 | not rated yet | 0
- Screening for abdominal aortic aneurysms indicated Feb 24, 2012 | not rated yet | 0
- Increased likelihood of male death from disease Jun 18, 2010 | not rated yet | 0
- Scientists find new mechanism by which cell signaling pathway contributes to rheumatoid arthritis development May 20, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be villous adenoma in colon, if there are no villi there
20 hours ago As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
- More from Physics Forums - Medical Sciences
More news stories
Every day, their baby stopped breathing, his collapsed bronchus blocking the crucial flow of air to his lungs. April and Bryan Gionfriddo watched helplessly, just praying that somehow the dire predictions ...
Medical research 10 hours ago | 5 / 5 (2) | 0
The human gut is loaded with commensal bacteria – "good" microbes that, among other functions, help the body digest food. The gastrointestinal tract contains literally trillions of such cells, and yet the ...
Medical research 14 hours ago | 5 / 5 (3) | 0 |
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
Medical research 14 hours ago | 4.9 / 5 (7) | 0 |
On May 22, JoVE will publish details of a technique to measure the health of human genetic material in relation to a patient's age. The method is demonstrated by the laboratory of Dr. Gil Atzmon at New York's Albert Einste ...
Medical research 17 hours ago | not rated yet | 0
(Medical Xpress)—Scientists supported by the National Institutes of Health have a new theory as to why a woman's fertility declines after her mid-30s. They also suggest an approach that might help slow ...
Medical research 19 hours ago | not rated yet | 0 |
Existing research shows that bicyclists who wear helmets have an 88 percent lower risk of brain injury, but researchers at Boston Children's Hospital found that simply having bicycle helmet laws in place showed a 20 percent ...
3 hours ago | not rated yet | 0
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
14 hours ago | 4.7 / 5 (3) | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
11 hours ago | 5 / 5 (2) | 2 |
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
11 hours ago | 4 / 5 (2) | 0 |
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
12 hours ago | not rated yet | 0 |
In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe ...
13 hours ago | 5 / 5 (1) | 0 |