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- Primary Contact: Tanya Lee Graf
- (859) 323-3467
- 741 South Limestone Street, Biomedical/Biological Sciences Research Building, Rm: B243, Lexington, KY 40536-0509
- Daugherty Lab
- Sunderland Polytechnic, UK, B.Sc. (Hons), 1978, Pharmacology
- University of Bath, UK, Ph.D., 1982, Pharmacology
- University of Bath, UK, Fellow, 1981-1982, Cardiol. Physiol.
- Washington University, St. Louis, MO, Fellow, 1982-1985, Atherosclerosis
- University of Bath, UK, D.Sc., 2002, Pharmacology
The Daugherty Lab is primarily focused on molecular mechanisms of human vascular diseases. Initially, the research was dedicated to modifications of lipoproteins and their roles in influencing the immune responses of atherosclerosis. Since arriving at the University of Kentucky in 1997, the lab has been focused on the role of the renin angiotensin system in atherosclerosis and aortic aneurysms. This work has been in close collaboration with the lab of Dr. Lisa Cassis. The group’s pioneer observation was that angiotensin II (AngII) infusion markedly promoted atherosclerosis and aortic aneurysms in hypercholesterolemic mice. We have subsequently published a series of articles in which we have routinely demonstrated profound effects and the related mechanisms of the renin angiotensin system on atherosclerosis and aortic aneurysms. The components of the renin angiotensin system we are interested in are the substrate, angiotensinogen, two critical enzymes (renin and angiotensin-converting enzyme), and one receptor (AngII type 1 receptor in humans and type 1a receptor in mice). To explore the molecular mechanisms by which AngII contributes to these vascular diseases, we focus on several inflammatory markers and lipoprotein metabolic regulators. During our research, we have developed many reagents including conditional cell specific deficient mice, vectors using adeno-associated virus and a pharmacological approach in antisense oligonucleotides. Some of our studies using mouse models have shown translational significance. Our study published in Journal of Clinical Investigation (2008; 118: 984-993) has led to the initiation of a clinical trial to determine the effects of renin inhibition (aliskiren) on preventing the progression of coronary atherosclerosis in humans measured by intravascular ultrasound (AQUARIUS). One of our ongoing stuies has demonstrated that inhibition of angiotensinogen not only prevents high blood pressure and atherosclerosis, but also ablates obesity. Based on these findings, a human antisense oligonucleotides targeting angiotensinogen has been developed and is awaiting approval for clinical trials.
NHLBI - Mechanisms of Thoracic Aortic Aneurysms; Alzheimer's Administrative Supplement
Role: PI
NHLBI - Mechanisms of Atherosclerosis: Production and action of AngII
Role: co-PI
AHA - AWRP Summer 2017 CENTER Strategically Focused Vascular Disease Research Network
Role: Center Director and PI of Project 1
NIH - Sex Differences in Angiotensis-Induced Vascular Disease
Role: Co-Investigator
NIH - Angiotensin: a Link Between Obesity and Hypertension.
Role: Co-Investigator
NIH/NCRR - Center of Research in Obesity and Cardiovascular Disease
Role: Mentor
Dr. Daugherty has over 317 publications with over 17,400 citations. To see the complete list of publications, follow the links below.
- Wu, CH ; Wang, Y.; Ma, M.; Mullick, AE ; Crooke, RM ; Graham, MJ ; Daugherty, A.; Lu, HS "Antisense oligonucleotides targeting angiotensinogen: insights from animal studies." Bioscience reports 39, 1 (2019): [PubMed Link] | [ Full text ]
- Daugherty, A. "Recipients of the 2019 Early Career Investigator Awards." Arteriosclerosis, thrombosis, and vascular biology (2019): ATVBAHA119312479. [PubMed Link] | [ Full text ]
- Huang, XF ; Zhang, SZ ; You, YY ; Zhang, N.; Lu, H.; Daugherty, A.; Xie, XJ "Ginkgo biloba extracts prevent aortic rupture in angiotensin II-infused hypercholesterolemic mice." Acta pharmacologica Sinica 40, 2 (2019): 192-198. [PubMed Link] | [ Full text ]
- Sawada, H.; Chen, JZ ; Wright, BC ; Sheppard, MB ; Lu, HS ; Daugherty, A. "Heterogeneity of Aortic Smooth Muscle Cells: A Determinant for Regional Characteristics of Thoracic Aortic Aneurysms?" Journal of translational internal medicine 6, 3 (2018): 93-96. [PubMed Link] |
- Lu, HS ; Schmidt, AM ; Hegele, RA ; Mackman, N.; Rader, DJ ; Weber, C.; Daugherty, A. "Reporting Sex and Sex Differences in Preclinical Studies." Arteriosclerosis, thrombosis, and vascular biology 38, 10 (2018): e171-e184. [PubMed Link] | [ Full text ]
- Hadi, T ; Boytard, L ; Silvestro, M ; Alebrahim, D ; Jacob, S ; Feinstein, J ; Barone, K ; Spiro, W ; Hutchison, S ; Simón, R.; Rateri, D.; Pinet, F ; Fenyö, D.; Adelman, M ; Moore, KJ ; Eltzschig, HK ; Daugherty, A.; Ramkhelawon, B. "Macrophage-derived netrin-1 promotes abdominal aortic aneurysm formation by activating MMP3 in vascular smooth muscle cells." Nature communications 9, 1 (2018): 5022. [PubMed Link] | [ Full text ]
- Sawada, H.; Wright, BC ; Chen, JZ ; Lu, HS ; Daugherty, A. "Drebrin: a new player in angiotensin II-induced aortopathies." Cardiovascular research 114, 13 (2018): 1699-1701. [PubMed Link] | [ Full text ]
- Au, DT ; Ying, Z.; Hernández-Ochoa, EO ; Fondrie, WE ; Hampton, B.; Migliorini, M ; Galisteo, R ; Schneider, MF ; Daugherty, A.; Rateri, DL ; Strickland, DK ; Muratoglu, SC "LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) Regulates Smooth Muscle Contractility by Modulating Ca<sup>2+</sup> Signaling and Expression of Cytoskeleton-Related Proteins." Arteriosclerosis, thrombosis, and vascular biology 38, 11 (2018): 2651-2664. [PubMed Link] | [ Full text ]
- Zheng, Z.; Ai, J.; Guo, L.; Ye, X.; Bondada, S.; Howatt, D.; Daugherty, A.; Li, XA "SR-BI (Scavenger Receptor Class B Type 1) Is Critical in Maintaining Normal T-Cell Development and Enhancing Thymic Regeneration." Arteriosclerosis, thrombosis, and vascular biology 38, 11 (2018): 2706-2717. [PubMed Link] | [ Full text ]
- Lutshumba, J.; Liu, S.; Zhong, Y.; Hou, T.; Daugherty, A.; Lu, H.; Guo, Z.; Gong, MC "Deletion of BMAL1 in Smooth Muscle Cells Protects Mice From Abdominal Aortic Aneurysms." Arteriosclerosis, thrombosis, and vascular biology 38, 5 (2018): 1063-1075. [PubMed Link] | [ Full text ]
- Kusters, PJH ; Seijkens, TTP ; Beckers, L.; Lievens, D.; Winkels, H.; Waard, V.; Duijvestijn, A.; Lindquist Liljeqvist, M.; Roy, J.; Daugherty, A.; Newby, A.; Gerdes, N.; Lutgens, E. "CD40L Deficiency Protects Against Aneurysm Formation." Arteriosclerosis, thrombosis, and vascular biology 38, 5 (2018): 1076-1085. [PubMed Link] | [ Full text ]
- Ren, L.; Sun, Y.; Lu, H.; Ye, D.; Han, L.; Wang, N.; Daugherty, A.; Li, F.; Wang, M.; Su, F.; Tao, W.; Sun, J.; Zelcer, N.; Mullick, AE ; Danser, AHJ ; Jiang, Y.; He, Y.; Ruan, X.; Lu, X. "(Pro)renin Receptor Inhibition Reprograms Hepatic Lipid Metabolism and Protects Mice From Diet-Induced Obesity and Hepatosteatosis." Circulation research 122, 5 (2018): 730-741. [PubMed Link] | [ Full text ]
- Wu, CH ; Daugherty, A.; Lu, H. "Multifaceted functions of macrophages in atherosclerosis." Current opinion in lipidology 29, 3 (2018): 275-276. [PubMed Link] | [ Full text ]
- Daugherty, A.; Lu, HS ; Hegele, RA ; Mackman, N.; Rader, DJ ; Schmidt, AM ; Weber, C. "Response by Daugherty et al to Letter Regarding Article, "Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies: A Statement From the <i>Arteriosclerosis, Thrombosis, and Vascular Biology</i> Council"." Arteriosclerosis, thrombosis, and vascular biology 38, 6 (2018): e101-e102. [PubMed Link] | [ Full text ]
- Wu, CH ; Mohammadmoradi, S.; Chen, JZ ; Sawada, H.; Daugherty, A.; Lu, HS "Renin-Angiotensin System and Cardiovascular Functions." Arteriosclerosis, thrombosis, and vascular biology 38, 7 (2018): e108-e116. [PubMed Link] | [ Full text ]
- Alsiraj, Y.; Thatcher, SE ; Blalock, E.; Fleenor, B.; Daugherty, A.; Cassis, LA "Sex Chromosome Complement Defines Diffuse Versus Focal Angiotensin II-Induced Aortic Pathology." Arteriosclerosis, thrombosis, and vascular biology 38, 1 (2018): 143-153. [PubMed Link] | [ Full text ]
- Ghoshal, S.; Stevens, JR ; Billon, C.; Girardet, C.; Sitaula, S.; Leon, AS ; Rao, DC ; Skinner, JS ; Rankinen, T.; Bouchard, C.; Nuñez, MV ; Stanhope, KL ; Howatt, DA ; Daugherty, A.; Zhang, J.; Schuelke, M.; Weiss, EP ; Coffey, AR ; Bennett, BJ ; Sethupathy, P.; Burris, TP ; Havel, PJ ; Butler, AA "Adropin: An endocrine link between the biological clock and cholesterol homeostasis." Molecular metabolism 8, (2018): 51-64. [PubMed Link] | [ Full text ]
- Ye, F.; Wang, Y.; Wu, C.; Howatt, DA ; Wu, CH ; Balakrishnan, A.; Mullick, AE ; Graham, MJ ; Danser, AHJ ; Wang, J.; Daugherty, A.; Lu, HS "Angiotensinogen and Megalin Interactions Contribute to Atherosclerosis." Arteriosclerosis, thrombosis, and vascular biology (2018): ATVBAHA118311817. [PubMed Link] | [ Full text ]
- Umebayashi, R.; Uchida, HA ; Kakio, Y.; Subramanian, V.; Daugherty, A.; Wada, J. "Cilostazol Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysms but Not Atherosclerosis in Apolipoprotein E-Deficient Mice." Arteriosclerosis, thrombosis, and vascular biology 38, 4 (2018): 903-912. [PubMed Link] | [ Full text ]
- Sawada, H.; Rateri, DL ; Moorleghen, JJ ; Majesky, MW ; Daugherty, A. "Smooth Muscle Cells Derived From Second Heart Field and Cardiac Neural Crest Reside in Spatially Distinct Domains in the Media of the Ascending Aorta-Brief Report." Arteriosclerosis, thrombosis, and vascular biology 37, 9 (2017): 1722-1726. [PubMed Link] | [ Full text ]
- Qing, H.; Jones, KL ; Heywood, EB ; Lu, H.; Daugherty, A.; Bruemmer, D. "Deletion of the NR4A nuclear receptor NOR1 in hematopoietic stem cells reduces inflammation but not abdominal aortic aneurysm formation." BMC cardiovascular disorders 17, 1 (2017): 271. [PubMed Link] | [ Full text ]
- Howatt, DA ; Dajee, M.; Xie, X.; Moorleghen, J.; Rateri, DL ; Balakrishnan, A.; Da Cunha, V.; Johns, DG ; Gutstein, DE ; Daugherty, A.; Lu, H. "Relaxin and Matrix Metalloproteinase-9 in Angiotensin II-Induced Abdominal Aortic Aneurysms." Circulation journal : official journal of the Japanese Circulation Society 81, 6 (2017): 888-890. [PubMed Link] | [ Full text ]
- Daugherty, A. "Recipients of the 2017 Early Career Investigator Awards." Arteriosclerosis, thrombosis, and vascular biology 37, 5 (2017): 737. [PubMed Link] | [ Full text ]
- Ye, F.; Wang, JA ; Daugherty, A.; Lu, H. "Macrophage-mediated mechanisms in atherosclerosis: still tangled." Current opinion in lipidology 28, 3 (2017): 286-287. [PubMed Link] | [ Full text ]
- Lu, H.; Daugherty, A. "Aortic Aneurysms." Arteriosclerosis, thrombosis, and vascular biology 37, 6 (2017): e59-e65. [PubMed Link] | [ Full text ]
- Daugherty, A.; Chen, Z.; Sawada, H.; Rateri, DL ; Sheppard, MB "Transforming Growth Factor-β in Thoracic Aortic Aneurysms: Good, Bad, or Irrelevant?" Journal of the American Heart Association 6, 1 (2017): [PubMed Link] | [ Full text ]
- Alsiraj, Y.; Thatcher, SE ; Charnigo, R.; Chen, K.; Blalock, E.; Daugherty, A.; Cassis, LA "Female Mice With an XY Sex Chromosome Complement Develop Severe Angiotensin II-Induced Abdominal Aortic Aneurysms." Circulation 135, 4 (2017): 379-391. [PubMed Link] | [ Full text ]
- Kim, HW ; Blomkalns, AL ; Ogbi, M.; Thomas, M.; Gavrila, D.; Neltner, BS ; Cassis, LA ; Thompson, RW ; Weiss, RM ; Lindower, PD ; Blanco, VM ; McCormick, ML ; Daugherty, A.; Fu, X.; Hazen, SL ; Stansfield, BK ; Huo, Y.; Fulton, DJ ; Chatterjee, T.; Weintraub, NL "Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine." American journal of physiology. Heart and circulatory physiology 313, 6 (2017): H1168-H1179. [PubMed Link] | [ Full text ]
- Wu, C.; Daugherty, A.; Lu, H. "A Color Segmentation-Based Method to Quantify Atherosclerotic Lesion Compositions with Immunostaining." Methods in molecular biology (Clifton, N.J.) 1614, (2017): 21-30. [PubMed Link] | [ Full text ]
- Lu, H.; Howatt, DA ; Balakrishnan, A.; Graham, MJ ; Mullick, AE ; Daugherty, A. "Hypercholesterolemia Induced by a PCSK9 Gain-of-Function Mutation Augments Angiotensin II-Induced Abdominal Aortic Aneurysms in C57BL/6 Mice-Brief Report." Arteriosclerosis, thrombosis, and vascular biology 36, 9 (2016): 1753-7. [PubMed Link] | [ Full text ]
- Lu, H.; Sheppard, M.; Daugherty, A. "Calcification in atherosclerotic lesions." Current opinion in lipidology 27, 5 (2016): 543-4. [PubMed Link] | [ Full text ]
- Liu, CL ; Wemmelund, H.; Wang, Y.; Liao, M.; Lindholt, JS ; Johnsen, SP ; Vestergaard, H.; Fernandes, C.; Sukhova, GK ; Cheng, X.; Zhang, JY ; Yang, C.; Huang, X.; Daugherty, A.; Levy, BD ; Libby, P.; Shi, GP "Asthma Associates With Human Abdominal Aortic Aneurysm and Rupture." Arteriosclerosis, thrombosis, and vascular biology 36, 3 (2016): 570-8. [PubMed Link] | [ Full text ]
- Sheppard, M.; Rateri, DL ; Daugherty, A. "miRs, miRs in the Wall, Who Is the Most Causative of Them All?" Journal of the American College of Cardiology 67, 25 (2016): 2978-80. [PubMed Link] | [ Full text ]
- Chen, X.; Howatt, DA ; Balakrishnan, A.; Moorleghen, JJ ; Wu, C.; Cassis, LA ; Daugherty, A.; Lu, H. "Angiotensin-Converting Enzyme in Smooth Muscle Cells Promotes Atherosclerosis-Brief Report." Arteriosclerosis, thrombosis, and vascular biology 36, 6 (2016): 1085-9. [PubMed Link] | [ Full text ]
- Daugherty, A.; Hegele, RA ; Mackman, N.; Rader, DJ ; Schmidt, AM ; Weber, C. "Complying With the National Institutes of Health Guidelines and Principles for Rigor and Reproducibility: Refutations." Arteriosclerosis, thrombosis, and vascular biology 36, 7 (2016): 1303-4. [PubMed Link] | [ Full text ]
- Lu, H.; Cassis, LA ; Kooi, CW ; Daugherty, A. "Structure and functions of angiotensinogen." Hypertension research : official journal of the Japanese Society of Hypertension 39, 7 (2016): 492-500. [PubMed Link] | [ Full text ]
- Sheppard, MB ; Daugherty, A.; Lu, H. "Insights into ascending aortic aneurysm pathogenesis using in vivo and ex vivo imaging systems in angiotensin II-infused mice." Journal of thoracic disease 8, 8 (2016): E822-4. [PubMed Link] | [ Full text ]
- Chen, X.; Rateri, DL ; Howatt, DA ; Balakrishnan, A.; Moorleghen, JJ ; Cassis, LA ; Daugherty, A. "TGF-β Neutralization Enhances AngII-Induced Aortic Rupture and Aneurysm in Both Thoracic and Abdominal Regions." PloS one 11, 4 (2016): e0153811. [PubMed Link] | [ Full text ]