BME Seminar - Wed., Jan. 22

Event Date: January 22, 2014
Time: 9:30 a.m.
Location: MJIS 1001, WL campus
Dr. Alan Daugherty, Senior Associate Dean for Research, College of Medicine and Director of the Saha Cardiovascular Research Center, University of Kentucky in Lexington will present a seminar entitled "Angiotensin peptides as mediators of abdominal and thoracic aortic aneurysms" on Wednesday, January 22nd, at 9:30 a.m. in MJIS 1001. The seminar will be teleconferenced to SL-220 at IUPUI (if room is available).

ABSTRACT: Infusion of angiotensin II (AngII) into normo- and hypercholesterolemic mice generates aortic aneurysms that are located in both the abdomonal and ascending regions.  While AngII promotes profound lumen dilation in both regions, the underlying mechanisms appear to differ markedly.  AngII-induced abdominal aortic aneurysms are initiated by a transmural medial disruption resulting in thrombus that is constrained within the adventitial.  Several types of inflammatory cells subsequently infiltrate the region of aortic rupture and result in dramatic tissue remodeling and progressive lumen expansion.  In contrast, AngII-induced ascending aortic aneurysms are characterized by progressive dilation associated with profound medial changes that predominate on the adventitial aspect of the aorta.  Continued expansion is not associated with profound infiltration of leukocytes into the aortic tissue.  In addition to overt location and pathological differences, increases in apoB-containing plasma lipoprotein concentrations augment AngII-induction of abdominal aneurysms, but have no effect on ascending aneurysms.  Conversely, increased blood pressure, per se, does not promote aneurysms in either region, as deduced from the lack of pathology in mice infused with norephinephrine at rates that increase systolic blood pressure to equivalent levels as observed during AngII-infusion.  Both pathologies are inhibited by administration of losartan or deletion of AT1a receptors.  Surprisingly, deletion of AT1a receptors in leukocytes, endothelial cells, or smooth muscle cells has no effect on either pathology.  The region-specific location of these two forms of aneurysms infers a mechanism located to the aortic wall.  However, there is currently no data demonstrating regional differences along the length of the aorta to AngII that provide insight into the location of the pathology.  Evolving clinical data is consistent with a role of AngII in human aortic aneurysms.  Therefore, determination of mechanisms of AngII-induced aneurysms should provide therapeutic insights.

Biography : Alan Daugherty was born in Liverpool, England. He completed his undergraduate studies in Pharmacology at Sunderland Polytechnic, and received both a Ph.D. and a D.Sc. from the University of Bath.  He moved to Washington University in St. Louis for fellowship training on lipoprotein metabolism and atherosclerosis. Subsequently, he was appointed to the faculty in the Division of Cardiovascular Medicine. He continued his studies on mechanisms of lipoprotein modification and immune function on the development of atherosclerosis. These studies also including imaging studies using chemical adducts for noninvasively detecting lipoprotein catabolism by a number of modalities. In 1997, he moved to the University of Kentucky in Lexington where he is now the Senior Associate Dean for Research in the College of Medicine and Director of the Saha Cardiovascular Research Center. Through the generosity of Linda and Jack Gill, he was also awarded the Gill Foundation Chair of Preventive Cardiology. Within the strong collaborative environment for cardiovascular research at the University of Kentucky, he has participated in studies on the role of angiotensin peptides in the development of atherosclerosis and aortic aneurysms.  He is highly committed to the research, advocacy, and educational missions of the American Heart Association.  He is currently a charter member of the Atherosclerosis and Inflammatory Cardiovascular System NIH study section. In July 2012, he had the privilege of becoming Editor-in-Chief of Arteriosclerosis, Thrombosis, and Vascular Biology (AVTB).

 

~BME Faculty Host: Craig Goergen~

***Coffee and juice will be provided at West Lafayette***