hlu4 | Saha Cardiovascular Research Center

09/1988-07/1993: MD, Zhejiang University College of Medicine, Hangzhou, China
04/2000-03/2003: PhD, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
04/2003-09/2007: Postdoctoral Fellow, University of Kentucky, Lexington, KY

Research Description:

Cardiovascular diseases are the leading cause of death in the nation and industrialized nations, accounting for nearly 50% of all deaths. Particularly, atherosclerosis is associated with significantly accelerated rates of cardiovascular complications. With the recognition of this evidence, understanding the mechanisms leading to these vascular diseases has become a focus of my research work. One promising medical therapy of atherosclerosis is the pharmacological inhibition of the renin angiotensin system. I am particularly interested in characterizing the renin angiotensin system by which mechanisms this system initiates and promotes the development of atherosclerosis in a hypercholesterolemic mouse model. While my research work has primarily focused on understanding the renin angiotensin system related mechanisms of atherosclerosis, I am also interested in the effects of the renin angiotensin system on aneurysm, which is the 13th leading cause of death in the United States. Understanding these mechanisms is of considerable interest as many members of the renin angiotensin system can be pharmacologically inhibited by agents already clinically used to treat hypertension in clinical patients. Since these drugs are currently being further investigated in large randomized trials for their efficacy to prevent and treat cardiovascular diseases, my research might point to molecular mechanisms by which these agents prevent the development of atherosclerosis and aneurysms.

Grants:

NHLBI-R01 (MPI: Lu/Daugherty) 05/01/2018-4/30/2022
Atherosclerosis Mechanisms: Angiotensin II production and action
Role: Contact PI (30% Efforts)

NHLBI-R35 (PI: Daugherty) 06/01/2021-06/30/2028
Determinant of Aorta Heterogeneity
Role: co-I (50% Efforts)

Selected Publications:

1. Lu H, Rateri DL, Feldman DL, Charnigo RJ, Fukamizu A, Ishida J, Oesterling EG, Cassis LA, Daugherty A. Renin inhibition reduces hypercholesterolemia-induced atherosclerosis. Journal of Clinical Investigation 2008; 118: 984-993.
2. Lu H, Cassis LA, Daugherty A. The role of the renin-angiotensin system in vascular aneurysm formation. Current Hypertension Reports 2008; 10: 99 - 106.
3. Wu CQ, Lu H, Cassis LA, Daugherty A. Molecular and pathophysiological features of angiotensinogen: a mini review. North America Journal of Medical Sciences 2011; 4: 196-203.
4. Lu H, Balakrishnan A, Howatt DA, Charnigo RJ, Liau G, Cassis LA, Daugherty A. Comparative effects of different modes of renin angiotensin system inhibition on hypercholesterolemia-induced atherosclerosis. British Journal of Pharmacology 2012; 165: 2000-2008.
5. Lu H, Rateri DL, Bruemmer D, Cassis LA, Daugherty A. Involvement of the renin-angiotensin system in abdominal and thoracic aortic aneurysms. Clinical Science 2012; 123: 531-543.
6. Lu H, Wu CQ, Howatt DA, Balakrishnan A, Charnigo RJ, Cassis LA, Daugherty A. Differential effects of dietary sodium intake on blood pressure and atherosclerosis. Journal of Nutritional Biochemistry 2013; 24: 49-53.
7. Lu H, Howatt D, Balakrishnan A, Moorleghen J, Rateri D, Daugherty A. Subcutaneous angiotensin II infusion using osmotic pumps induces aortic aneurysms in mice. Journal of Visualized Experiments 2015; 103.
8. Chen X, Howatt DA, Balakrishnan A, Moorleghen JJ, Wu C, Cassis LA, Daugherty A, Lu H. Angiotensin-conveting enzyme in smooth muscle cells promotes atherosclerosis. Arteriosclerosis, Thrombosis and Vascular Biology. 2016; 36: 1085-1089.
9. 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. Arteriosclerosis, Thrombosis and Vascular Biology. 2016; 36: 1753-1757.
10. Howatt DA, Dajee M, Xie X, Moorleghen JJ, 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. 2017; 81: 888-890.
https://www.ncbi.nlm.nih.gov/sites/myncbi/143PDNDsrP6/bibliography/43819...

PubMed Publications:

Ikezoe, T ; Shoji, T.; Guo, J.; Shen, F.; Lu, HS ; Daugherty, A.; Nunokawa, M ; Kubota, H ; Miyata, M ; Xu, B.; Dalman, RL "No Effect of Hypercholesterolemia on Elastase-Induced Experimental Abdominal Aortic Aneurysm Progression." Biomolecules 11, 10 (2021): [PubMed Link] | [ Full text ]
Sawada, H.; Daugherty, A.; Lu, HS "From unbiased transcriptomics to understanding the molecular basis of atherosclerosis." Current opinion in lipidology 32, 5 (2021): 328-329. [PubMed Link] | [ Full text ]
Chen, JZ ; Sawada, H.; Ye, D.; Katsumata, Y.; Kukida, M ; Ohno-Urabe, S ; Moorleghen, JJ ; Franklin, MK ; Howatt, DA ; Sheppard, MB ; Mullick, AE ; Lu, HS ; Daugherty, A. "Deletion of AT1a (Angiotensin II Type 1a) Receptor or Inhibition of Angiotensinogen Synthesis Attenuates Thoracic Aortopathies in Fibrillin1C1041G/+ Mice." Arteriosclerosis, thrombosis, and vascular biology 41, 10 (2021): 2538-2550. [PubMed Link] | [ Full text ]
Cui, H.; Chen, Y.; Li, K.; Zhan, R.; Zhao, M.; Xu, Y.; Lin, Z.; Fu, Y.; He, Q.; Tang, PC ; Lei, I ; Zhang, J.; Li, C.; Sun, Y.; Zhang, X.; Horng, T ; Lu, HS ; Chen, YE ; Daugherty, A.; Wang, D.; Zheng, L. "Untargeted metabolomics identifies succinate as a biomarker and therapeutic target in aortic aneurysm and dissection." European heart journal 42, 42 (2021): 4373-4385. [PubMed Link] | [ Full text ]
Kukida, M ; Cai, L.; Ye, D.; Sawada, H.; Katsumata, Y.; Franklin, MK ; Hecker, PI ; Campbell, KS ; Danser, AHJ ; Mullick, AE ; Daugherty, A.; Temel, RE ; Lu, HS "Renal Angiotensinogen Is Predominantly Liver Derived in Nonhuman Primates." Arteriosclerosis, thrombosis, and vascular biology 41, 11 (2021): 2851-2853. [PubMed Link] | [ Full text ]
Kukida, M ; Sawada, H.; Ohno-Urabe, S ; Howatt, DA ; Moorleghen, JJ ; Poglitsch, M ; Daugherty, A.; Lu, HS "Effects of Endogenous Angiotensin II on Abdominal Aortic Aneurysms and Atherosclerosis in Angiotensin II-Infused Mice." Journal of the American Heart Association 10, 9 (2021): e020467. [PubMed Link] | [ Full text ]
Davis, FM ; Tsoi, LC ; Melvin, WJ ; denDekker, A ; Wasikowski, R ; Joshi, AD ; WOLF, S.; Obi, AT ; Billi, AC ; Xing, X.; Audu, C ; Moore, BB ; Kunkel, SL ; Daugherty, A.; Lu, HS ; Gudjonsson, JE ; Gallagher, KA "Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms." The Journal of experimental medicine 218, 6 (2021): [PubMed Link] | [ Full text ]
Ohno-Urabe, S ; Kukida, M ; Franklin, MK ; Katsumata, Y.; Su, W.; Gong, MC ; Lu, HS ; Daugherty, A.; Sawada, H. "Authentication of In Situ Measurements for Thoracic Aortic Aneurysms in Mice." Arteriosclerosis, thrombosis, and vascular biology 41, 6 (2021): 2117-2119. [PubMed Link] | [ Full text ]
Alsiraj, Y.; Thatcher, SE ; Blalock, E.; Saintilnord, WN ; Daugherty, A.; Lu, HS ; Luo, W.; Shen, YH ; Lemaire, SA ; Arnold, AP ; Cassis, LA "Monosomy X in Female Mice Influences the Regional Formation and Augments the Severity of Angiotensin II-Induced Aortopathies." Arteriosclerosis, thrombosis, and vascular biology 41, 1 (2021): 269-283. [PubMed Link] | [ Full text ]
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Rica, Cebollada ; Cecarini, V ; Cecconi, F.; Cechowska-Pasko, M ; Cenci, S.; Ceperuelo-Mallafré, V ; Cerqueira, JJ ; Cerutti, JM ; Cervia, D.; Cetintas, VB ; Cetrullo, S.; Chae, HJ ; Chagin, AS ; Chai, CY ; Chakrabarti, G.; Chakrabarti, O ; Chakraborty, T.; Chakraborty, T.; Chami, M ; Chamilos, G.; Chan, DW ; Chan, EYW ; Chan, ED ; Chan, HYE ; Chan, HH ; Chan, H.; Chan, MTV ; Chan, YS ; Chandra, PK ; Chang, CP ; Chang, C.; Chang, HC ; Chang, K.; Chao, J.; Chapman, T ; Charlet-Berguerand, N ; Chatterjee, S.; Chaube, SK ; Chaudhary, A.; Chauhan, S.; Chaum, E ; Checler, F ; Cheetham, ME ; Chen, CS ; Chen, GC ; Chen, JF ; Chen, LL ; Chen, L.; Chen, L.; Chen, M.; Chen, MK ; Chen, N.; Chen, Q.; Chen, RH ; Chen, S.; Chen, W.; Chen, W.; Chen, XM ; Chen, XW ; Chen, X.; Chen, Y.; Chen, YG ; Chen, Y.; Chen, Y.; Chen, YJ ; Chen, YQ ; Chen, ZS ; Chen, Z.; Chen, ZH ; Chen, ZJ ; Chen, Z.; Cheng, H.; Cheng, J.; Cheng, SY ; Cheng, W.; Cheng, X.; Cheng, XT ; Cheng, Y.; Cheng, Z.; Chen, Z.; Cheong, H.; Cheong, JK ; 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Csizmadia, T ; Cuadrado, A ; Cui, B.; Cui, J.; Cui, Y.; Cui, Y.; Culetto, E ; Cumino, AC ; Cybulsky, AV ; Czaja, MJ ; Czuczwar, SJ ; D'Adamo, S ; D'Amelio, M.; D'Arcangelo, D ; D'Lugos, AC ; D'Orazi, G.; da Silva, JA ; Dafsari, HS ; Dagda, RK ; Dagdas, Y ; Daglia, M ; Dai, X.; Dai, Y.; Dai, Y.; Dal Col, J ; Dalhaimer, P ; Dalla Valle, L.; Dallenga, T ; Dalmasso, G.; Damme, M.; Dando, I ; Dantuma, NP ; Darling, AL ; Das, H.; Dasarathy, S.; Dasari, SK ; Dash, S.; Daumke, O ; Dauphinee, AN ; Davies, JS ; Dávila, VA ; Davis, RJ ; Davis, T.; Dayalan Naidu, S.; De Amicis, F ; De Bosscher, K ; De Felice, F ; De Franceschi, L.; De Leonibus, C ; Barbosa, MG de Mattos; De Meyer, GRY ; De Milito, A.; De Nunzio, C.; De Palma, C ; De Santi, M.; De Virgilio, C ; De Zio, D.; Debnath, J.; DeBosch, BJ ; Decuypere, JP ; Deehan, MA ; Deflorian, G ; DeGregori, J ; Dehay, B.; Del Rio, G ; , ; Delbridge, LMD ; Delorme-Axford, E.; Delpino, MV ; Demarchi, F.; Dembitz, V ; Demers, ND ; Deng, H.; Deng, Z.; Dengjel, J.; Dent, P.; Denton, D.; DePamphilis, ML ; Der, CJ ; Deretic, V.; Descoteaux, A.; Devis, L ; Devkota, S ; Devuyst, O ; Dewson, G ; Dharmasivam, M ; Dhiman, R ; di Bernardo, D ; Di Cristina, M ; Di Domenico, F.; Di Fazio, P ; Di Fonzo, A ; Di Guardo, G ; Di Guglielmo, GM ; Di Leo, L ; Di Malta, C ; Di Nardo, A.; Di Rienzo, M ; Di Sano, F ; Diallinas, G ; Diao, J.; Díaz-Araya, G.; Díaz-Laviada, I.; Dickinson, JM ; Diederich, M.; Dieudé, M ; Dikic, I.; Ding, S.; Ding, WX ; Dini, L.; Dinić, J ; Dinic, M ; Dinkova-Kostova, AT ; Dionne, MS ; Distler, JHW ; Diwan, A.; Dixon, IMC ; Djavaheri-Mergny, M.; Dobrinski, I ; Dobrovinskaya, O ; Dobrowolski, R ; Dobson, RCJ ; Đokić, J ; Emre, Dokmeci ; Donadelli, M.; Dong, B.; Dong, X.; Dong, Z.; Ii, GW Dorn; Dotsch, V ; Dou, H.; Dou, J.; Dowaidar, M ; Dridi, S.; Drucker, L.; Du, A ; Du, C.; Du, G.; Du, HN ; Du, LL ; Toit, A.; Duan, SB ; Duan, X.; Duarte, SP ; Dubrovska, A ; Dunlop, EA ; Dupont, N.; Durán, RV ; Dwarakanath, BS ; Dyshlovoy, SA ; Ebrahimi-Fakhari, D.; Eckhart, L.; Edelstein, CL ; Efferth, T ; Eftekharpour, E ; Eichinger, L.; Eid, N ; Eisenberg, T.; Eissa, NT ; Eissa, S ; Ejarque, M ; Andaloussi, El ; El-Hage, N.; El-Naggar, S ; Eleuteri, AM ; El-Shafey, ES ; Elgendy, M.; Eliopoulos, AG ; Elizalde, MM ; Elks, PM ; Elsasser, HP ; Elsherbiny, ES ; Emerling, BM ; Emre, NCT ; Eng, CH ; Engedal, N.; Engelbrecht, AM ; Engelsen, AST ; Enserink, JM ; Escalante, R.; Esclatine, A.; Escobar-Henriques, M ; Eskelinen, EL ; Espert, L.; Eusebio, MO ; Fabrias, G.; Fabrizi, C.; Facchiano, A.; Facchiano, F ; Fadeel, B.; Fader, C ; Faesen, AC ; Fairlie, WD ; Falcó, A ; Falkenburger, BH ; Fan, D.; Fan, J.; Fan, Y.; Fang, EF ; Fang, Y.; Fang, Y.; Fanto, M.; Farfel-Becker, T ; Faure, M.; Fazeli, G ; Fedele, AO ; Feldman, AM ; Feng, D.; Feng, J.; Feng, L.; Feng, Y.; Feng, Y.; Feng, W.; Araujo, Fenz ; Ferguson, TA ; Fernández, Á.F.; Fernandez-Checa, JC ; Fernández-Veledo, S ; Fernie, AR ; AW, Ferrante ; Ferraresi, A ; Ferrari, MF ; Ferreira, JCB ; Ferro-Novick, S.; Figueras, A ; Filadi, R ; Filigheddu, N ; Filippi-Chiela, E ; Filomeni, G.; Fimia, GM ; Fineschi, V ; Finetti, F ; Finkbeiner, S.; Fisher, EA ; Fisher, PB ; Flamigni, F.; Fliesler, SJ ; Flo, TH ; Florance, I ; Florey, O.; Florio, T ; Fodor, E ; Follo, C.; Fon, EA ; Forlino, A ; Fornai, F.; Fortini, P ; Fracassi, A ; Fraldi, A.; Franco, B ; Franco, R.; Franconi, F.; Frankel, LB ; Friedman, SL ; Fröhlich, LF ; Frühbeck, G ; Fuentes, JM ; Fujiki, Y ; Fujita, N.; Fujiwara, Y.; Fukuda, M.; Fulda, S.; Furic, L ; Furuya, N ; Fusco, C.; Gack, MU ; Gaffke, L ; Galadari, S.; Galasso, A ; Galindo, MF ; Kankanamalage, Gallolu ; Galluzzi, L.; Galy, V.; Gammoh, N.; Gan, B ; Ganley, IG ; Gao, F.; Gao, H.; Gao, M.; Gao, P.; Gao, SJ ; Gao, W.; Gao, X.; Garcera, A ; Garcia, MN ; Garcia, VE ; Del Portillo, García- ; Garcia-Escudero, V ; Garcia-Garcia, A ; Garcia-Macía, M.; García-Moreno, D ; Garcia-Ruiz, C.; García-Sanz, P ; Garg, AD ; Gargini, R.; Garofalo, T ; Garry, RF ; Gassen, NC ; Gatica, D.; Ge, L.; 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Lu, HS ; Kukida, M ; Daugherty, A. "Links lipoproteins to chronic kidney disease and atherosclerosis." Current opinion in lipidology 30, 5 (2019): 410-411. [PubMed Link] | [ Full text ]
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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 ]
Robinet, P.; Milewicz, DM ; Cassis, LA ; Leeper, NJ ; Lu, HS ; Smith, JD "Consideration of Sex Differences in Design and Reporting of Experimental Arterial Pathology Studies-Statement From ATVB Council." Arteriosclerosis, thrombosis, and vascular biology 38, 2 (2018): 292-303. [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 ]
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 ]
Wang, C.; Chen, H.; Zhu, W.; Xu, Y.; Liu, M.; Zhu, L.; Yang, F.; Zhang, L.; Liu, X.; Zhong, Z.; Zhao, J.; Jiang, J.; Xiang, M.; Yu, H.; Hu, X.; Lu, H.; Wang, J. "Nicotine Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells." Arteriosclerosis, thrombosis, and vascular biology 37, 1 (2017): 53-65. [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 ]
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 ]
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] |
Lu, H.; Wu, C.; Howatt, DA ; Balakrishnan, A.; Moorleghen, JJ ; Chen, X.; Zhao, M.; Graham, MJ ; Mullick, AE ; Crooke, RM ; Feldman, DL ; Cassis, LA ; Vander Kooi, CW ; Daugherty, A. "Angiotensinogen Exerts Effects Independent of Angiotensin II." Arteriosclerosis, thrombosis, and vascular biology 36, 2 (2016): 256-65. [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 ]