UCLA researchers in the Department of Anesthesiology have developed novel inhibitors of miRNA-192-5P for the treatment of abdominal aortic aneurysms.
BACKGROUND:
Abdominal aortic aneurysm (AAA) occurs when the lower part of the major vessel that distributes blood to the body, the aorta, becomes weakened and enlarged. A weakened andenlarged aorta may eventually burst, causing severe, life threatening bleeding. The only current medical treatment for AAA is surgical correction of aneurysms larger than 5.5 cm, which are often not diagnosed early enough to stop disease progression and aortic rupture. UCLA researchers have previously identified a novel circulating biomarker used for early diagnosis and monitoring of AAA. However, there are still no existing therapeutics to attenuate the progression of AAA.
INNOVATION:
Using a robust model of Angiotensin II (Ang II) infused hph-1 mice, UCLA researchers have developed novel suppressors of miRNA-192-59 to inhibit aortic dilation and ultimately serve as effective treatment for abdominal aortic aneurysms. Treatment with these miRNA-192-59 inhibitors lessened AAA development by reducing elastin breakdowns, adventitial hypertrophy and intra-wall thrombosis to maintain the vascular hemostasis and integrity. Further, ROS production and eNOS uncoupling activity were also mitigated, which are typical markers of aortic aneurysms as demonstrated by various classical studies from the group (i.e. Gao L et al, Hypertension 2012, collected by Faculty 1000 to be ub the top 2% of Biology and Medicine). These inhibitors will serve as first in class therapeutics for the mitigation of AAA, from which many additional drugs may be modeled after.
POTENTIAL APPLICATIONS:
• Treatment of abdominal aortic aneurysms
ADVANTAGES:
• Attenuated aneurysm formation characterized by decreased aortic size
• Decreased vascular matrix degradation, eNOS uncoupling activity, and ROS production
• First in class novel inhibitors that may be further modified to increase their efficacy
DEVELOPMENT-TO-DATE:
The novel inhibitors have been demonstrated to be effective in mice.