Alan Daugherty, Ph.D.

SAHA Cardiovascular Research Center
University of Kentucky

From left to right: Kyung Sik Jung, Hong Lu,  Congqing Wu, Jing Liu, Venkat Subramanian, Frank Davis, Debra Rateri, Deborah Howatt, Alan Daugherty, Anju Balakrishnan, Jessica Moorleghen

Primary Research:
The primary focus of the laboratory is to delineate the role of the renin-angiotensin system on vascular pathology. In collaboration with the laboratory of Dr. Lisa Cassis during the early days of arriving at the University of Kentucky, initial studies examined the role of blood pressure in atherosclerosis. These studies demonstrated that infusion of angiotensin II greatly augmented the size of atherosclerotic lesions in hypercholesterolemic mice. Serendipitously, it was observed that angiotensin II infusion promoted development of both abdominal and ascending aortic aneurysms. The aneurysms in these two aortic regions have distinctive appearances and pathologies. Investigations have been facilitated by development of a large number of reagents, including mice that have floxed genes: (A) AT1a receptor, the major receptor angiotensin II, (B) angiotensinogen, the unique source of all angiotensin peptides, and (C) ACE, a major rate limiting enzyme in the synthesis of angiotensin II. These studies are performed with many collaborative interactions at the University of Kentucky.

Lab Members:
Debra Rateri, Scientist
Deborah Howatt, Senior Research Analyst
Jessica Moorleghen, Research Analyst
Anju Balakrishnan, Research Analyst
Hong Lu, Research Assistant Professor
Congqing Wu, Graduate Student, AHA Fellow
Jing Lui, Graduate Student
Frank Davis, Medical Student, Sarnoff Fellow

Number of trainees in the laboratory: 3

Laboratory Web site:

https://cvrc.med.uky.edu/daugherty-lab

Recent Publications:

Chen X, Lu H, Zhao M, Tashiro K, Cassis LA, Daugherty A. Contributions of leukocytic angiotensin-converting enzyme to the development of atherosclerosis. Arterioscler Thromb Vasc Biol. 33.2075-2080, 2013

Xie X, Lu H, Moorleghen JJ, Howatt DA, Rateri DL, Cassis LA, Daugherty A. Doxycycline does not influence established abdominal aortic aneurysms in angiotensin II-infused mice. PLoS One. 7: e46411, 2012

Lu H, Balakrishnan A, Howatt DA, Wu C, Charnigo R, Liau G, Cassis LA, Daugherty A. Comparative effects of different modes of renin angiotensin system inhibition on hypercholesterolemia-induced atherosclerosis. Brit J Pharmacol. 165:2000-2008, 2011

Rateri DL, Howatt DA, Moorleghen JJ, Charnigo R, Cassis LA, Daugherty A. Prolonged infusion of angiotensin II in apoE(-/-) mice promotes macrophage recruitment with continued expansion of abdominal aortic aneurysm. Am J Pathol 179: 1542-1548, 2011

Rateri DL, Moorleghen JJ, Balakrishnan A, Owens AP III, Howatt DA, Subramanian V, Poduri A, Charnigo R, Cassis LA, Daugherty LA. Endothelial cell-specific deficiency of AngII type 1a receptors attenuates angII-induced thoracic aortic aneurysms in LDL receptor -/- mice. Circ Res. 108: 574-581, 2011