Aortic Aneurysm Research Program | Dr. Gorav Ailawadi
Aortic aneurysms and dissections are the 15th leading cause of death in the U.S. There is no proven medical therapy to treat or prevent aortic aneurysms. Thus, understanding molecular mechanisms of aneurysm formation are critical to developing novel treatments. There is evidence that local inciting events of unknown nature lead to upregulation of inflammatory cytokines, leukocyte infiltration into the aortic wall, smooth muscle cell (SMC) proliferation, upregulation of matrix metalloproteinases (MMPs) by leukocytes and SMCs. These alterations lead to destruction of the aortic wall. (Figure 1) In late stages of aneurysm progression, SMCs undergo apoptosis, thereby eliminating the cells that are the primary source of extracellular matrix proteins necessary for mechanical stabilization of the blood vessel, thus increasing the risk of aneurysm rupture. To date, studies have primarily focused on the role of leukocytes in aneurysm development, while little is known of the role of SMCs.
Our lab has over 25 years combined experience in investigating aneurysms. In addition to a robust lab studying abdominal aortic aneurysms (AAA- LINK), we have developed expertise in thoracic aortic aneurysms (TAA). TAAs are distinct from other aneurysms with many patients having a genetic component. Also, repairing the thoracic aorta has greater risks than diseases of other blood vessels making investigation extremely important.
We have developed novel models of thoracic aneurysm formation in mice and have determined critical roles for several pathways including IL-1 beta, IL-6, and KLF4 (Kruppel Like Factor 4).
- NIH grant number: R01 HL126668 (with Dr. Ailawadi as the Principle Investigator
- NIH, NHLBI 1K08HL098560-01, The Effects of KLF4 in Experimental Aortic Aneurysm Formation, 12/1/09-11/30/14
- Thoracic Surgery Foundation for Research and Education Research Grant The Effects of IL-1 Beta on Smooth Muscle Cell Phenotype During Experimental Aortic Aneurysm Formation 7/1/08-6/30/10
- Coulter Translational Research Program, University of Virginia, Biomedical Engineering Therapeutic Modification of Myocardial Infarct Anisotropy, Role: Co-PI, 4/01/08-/31/09
- Coulter Translational Research Program, University of Virginia, Biomedical Engineering Determination of the Need for Blood Platelet Transfusion During Cardiopulmonary Bypass Surgery with an Ultrasound-Based Technique for Real-time Blood Viscosity Estimation, Role: Co-PI, 4/01/08-3/30/10
- Partner’s Fund, University of Virginia The Effects of IL-1B on Smooth Muscle Cell Phenotypic Switching in Experimental Aortic Aneurysm Formation, Role: PI, 10/1/07-6/30/08