A gene that contributes to cancer and cardiovascular development may be the cause of swelling in the most common type of aortic aneurysm, and could be the key to treatment.
This new study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, is the first of its kind to show Notch 1 signaling is triggered in abdominal aortic aneurysmal tissue in humans and mice.
The largest blood vessel in the body is the aorta. An abdominal aortic aneurysm (AAA), the most common form of aortic aneurysms, happen when the weakened aortic wall enlarges in the abdominal part of the vessel. A previous study has identified that the LRP1 gene is uniquely associated with AAA.
AAA is a leading cause of death in the United States among men over the age of 65, and this disease is caused by high blood pressure, high cholesterol, and smoking.
Although it is rare in children, it can occur in those who have connective tissue diseases or have experienced a blunt trauma. Less than 20 percent of patients will survive a ruptured aneurysm and as of now, surgery is the only treatment option available for AAA.
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, says: “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.”
Inflammation is a tell-tale sign of AAA. The Notch 1 gene contributes in many developmental processes in humans and previous studies have showed its signaling road to be active in many inflammatory diseases.
The study’s lead author, Chetan Hans, PhD, principal investigator in the Center for Cardiovascular and Pulmonary Research at Nationwide Children’s Hospital says, “Notch 1 signaling is a significant regulator of the inflammatory response. However, its role in AAA is unknown.”
To study the role of Notch 1 signaling in AAA development, Dr. Hans and his team examined tissue specimens from the abdominal aorta of patients undergoing AAA repair and a mouse model of the disease. They proved for the first time that Notch 1 signaling is triggered in these models and in human patients.
Then the researchers analyzed the role Notch 1 signaling plays in the Angiotensin II-induced mouse model of AAA, when Notch 1 signaling is hindered.
Results showed that mice that had a genetic shortage of Notch 1 or acquired a chemical Notch inhibitor had less inflammation in the aorta and had a decreased prevalence of AAA.
Dr. Hans concludes:
“Our data suggest that Notch 1 is an important player in the inflammatory process in the setting of AAA. Treatment with Notch 1-specific inhibitors may be a potentially promising strategy for slowing aneurysm development.”
The authors recommend further studies to understand the exact role of these inflammatory factors in AAA.
Written by Kelly Fitzgerald