Aortic Disease Research Laboratory
Under the supervision of Ying H. Shen, M.D., Ph.D. and Scott A. LeMaire, M.D., director of research for the Division and Vice Chair for Research in the Department, the cardiac surgery research team pursues several research projects and maintains one of the world’s most extensive and well-cataloged aortic tissue banks.
This core resource facilitates investigations into the causes and progression of aortic disease pursued by our researchers, as well as researchers from other academic institutions.
Detrimental effects of ciprofloxacin on the aortic wall
Despite concerns raised by population-based cohort studies, the U.S. FDA determined that there was not sufficient evidence to issue a warning that fluoroquinolone use increases the risk of aortic aneurysm, dissection, and rupture. To address the gap in evidence, Drs. LeMaire and Shen conducted experiments to test the hypothesis that ciprofloxacin impairs aortic homeostasis and renders the aortic wall susceptible to stress-induced development of aortic aneurysm and dissection.
In an established mouse model of aortic disease, they found that ciprofloxacin significantly increased susceptibility to challenge-induced aortic dissection and rupture compared to controls. They also found that ciprofloxacin decreased lysyl oxidase expression and activity, increased matrix metalloproteinase levels and activity, and increased elastic fiber fragmentation and cell injury. These findings supported concerns raised in observational clinical studies and suggested that the drug should be used with caution in patients with aortic dilatation and those at high risk for aortic aneurysm and dissection.
In October 2018, shortly after publication of these results, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency cited the paper in their announcement warning that fluoroquinolones increase the risk of aortic aneurysm and dissection. In December 2018, the U.S. FDA published a similar warning.
Laboratory for Cardiac Regeneration
Researchers in the Laboratory for Cardiac Regeneration are studying whether cellular reprogramming can be applied to improve cardiac infarct remodeling and function by testing the serial hypotheses that: a) inadequate up-regulation of requisite reprogramming genes limits cell transdifferentiation efficiency, which can be optimized beyond current thresholds via the comprehensive application of genomic activation strategies, b) that the density of (contractile) iCMs in infarct zones as well as indirect or paracrine (i.e., antifibrotic) mechanisms play critical roles in GMT/VEGF mediated infarct remodeling, and c) that cardiac fibroblasts can be made susceptible to reprogramming in a clinically relevant fashion.
Valve Sparing Approach to Aortic Repair
Under the leadership of Joseph S. Coselli, M.D, the division is active in evaluating the outcomes of both standard and emerging surgical techniques for aortic repair. While the traditional approach toward repair of an aortic root aneurysm involves replacing it with a composite valve graft, an alternate approach—valve-sparing aortic root replacement—has increasingly become more widely used.
The valve-sparing approach maintains the superior hemodynamics of the native aortic valve and replaces the surrounding aneurysmal aorta with graft material. However, the primary advantage of valve-sparing repair is the avoidance of long-term anticoagulant therapy, which necessitates an often intolerable change in lifestyle.
In this illustration, valve-sparing aortic root replacement is demonstrated in a patient with an aortic root aneurysm (A). (B) The ascending aorta is opened and the diseased tissue is removed. (C) A graft is sewn to the aorta. (D) The aortic valve is prepared. (E) The replacement graft is brought down onto the native valve. (F-H) The aortic valve is secured to the graft. (I) The left main coronary artery is attached to the graft. (J) The top graft is attached to the bottom graft. (K) The right coronary artery is attached to the graft. (L) The completed repair is shown.
NIH T32 Research Training Program in Cardiovascular Surgery
Our NIH-funded T32 aims to increase the pool of M.D.s and Ph.D.s who enter cardiovascular surgical research careers, and provide our trainees with the skills necessary to be successful and productive in cardiovascular research. Learn about our T32 training program in cardiovascular surgery research.