Welcome to the Cai Laboratory! We belong to the Division of Molecular Medicine, UCLA Department of Anesthesiology & Perioperative Medicine. We are also part of the Cardiovascular Research Laboratories and the Department of Medicine, Division of Cardiology. As the principal investigator of the group, I appreciate your visiting our webpage and hope that you find our research exciting. You can also read more about our team here.
We are interested in reactive oxygen species regulation of endothelial nitric oxide synthase (eNOS) expression and function, and its consequences regarding nitric oxide bioavailability and development of cardiovascular diseases. Nitric oxide is an important signaling molecule. It relaxes vascular smooth muscle to dilate blood vessels. It also inhibits a variety of pathological events such as activation of platelets and induction of inflammatory proteins. Loss of nitric oxide leads to high blood pressure and atherosclerotic vascular disease. It is of great clinical significance to understand the regulation of nitric oxide bioavailability at molecular levels.
Data accumulated in the past decade have shown that production of reactive oxygen species increases during the biological processes of aging, and that oxidative stress is implicated in the pathogenesis of cardiovascular and pulmonary diseases, cancer, and neurodegenerative disorders. An important consequence of excessive production of reactive oxygen species is the oxidative inactivation of nitric oxide. For example, superoxide radicals rapidly react with nitric oxide to form peroxynitrite, resulting in immediate loss of nitric oxide. Additional studies suggest that reactive oxygen species can oxidize tetrahydrobiopterin, an essential cofactor for eNOS. This response leads to a condition where eNOS produces superoxide rather than nitric oxide. This "uncoupling" phenomenon of eNOS likely prolongs oxidative stress. Our goal is to characterize in-depth molecular mechanisms whereby eNOS uncouples under disease states. This will ultimately lead to discovery of novel therapeutics restoring nitric oxide production from uncoupled eNOS -- in other words, "recoupling" of eNOS. One focus in the lab is to explore molecular mechanisms and consequences of eNOS uncoupling in various forms of vascular diseases such as hypertension, abdominal aortic aneurysm, atherosclerosis, and diabetic vascular disease, using a combination of molecular and cell biological, genetic and physiological approaches.
We are also interested in defining:
Hua Linda Cai, MD, PhD, holds the rank of Professor in the Departments of Medicine and of Anesthesiology & Perioperative Medicine. She also serves as Director for Translational Research in the Department of Anesthesiology & Perioperative Medicine. She received her MD degree from the Medical College of Qingdao University, China, and her PhD from the University of New South Wales, Sydney, Australia and Emory University, Atlanta, Georgia.
For a full list of Dr. Cai's publications, please click here.
Siu KL, Gao L, Cai H. Differential roles of protein complexes NOX1-NOXO1 and NOX2-p47phox in mediating endothelial redox responses to oscillatory and unidirectional laminar shear stress. (2016) J. Biol. Chem. 291(16):8653-62. PMCID: PMC4861435.
This article reports differential roles of different NADPH oxidase complexes in mediating endothelial redox responses to the protective laminar shear stress or the atherogenic oscillatory shear stress.
Sun H, Olson K, Chen G, Prosdocimo DA, Zhou M, Wang Z, Zeyaraj D, Youn JY, Ren S, Shah S, Newgard C, Cai H, Ping P, Schulze PC, Lynch C, Jain MK, Wang YB. Catabolic Defect of Branched-Chain Amino Acids Promotes Heart Failure. (2016) Circulation. 133(21):2038-49. PMCID: PMC4879058.
The article reports a novel role of branched-chain amino acids in the pathogenesis of heart failure.
Wu J, Saleh MA, Kirabo A, Itani HA, Montaniel KR, Xiao L, Chen W, Mernaugh RL, Cai H, Bernstein KE, Goronzy JJ, Weyand CM, Curci JA, Barbaro NR, Moreno H, Davies SS, Roberts LJ 2nd, Madhur MS, Harrison DG. Immune activation caused by vascular oxidation promotes fibrosis and hypertension. (2016) J. Clin. Invest. 126(1):50-67. PMCID: PMC4701546.
This article reports that vascular oxidative stress promotes immune activation to mediate fibrosis and development of hypertension.
Zhang Y, Li Q, Youn JY, Cai H. PTP1B in calpain-dependent feedback regulation of VEGFR2 in endothelial cells: implication in VEGF-dependent angiogenesis and diabetic wound healing. (2017) J. Biol. Chem. 13;292(2):407-416.
This article reports a novel calpain/PTP1B/VEGFR2 feedback regulation to prevent VEGFR2 over-activation. Activation of the primary calpain/PI3K/AMPK/Akt/eNOS signaling to induce NO production, or to attenuate PTP1B to potentiate VEGFR2 signaling, is highly effective in promoting diabetic wound healing.
Siu KL*, Li Q*, Zhang YX, Guo J, Youn JY, Du J, Cai H. NOX isoforms in the development of abdominal aortic aneurysm. (2017) Redox Biology. 11:118-125. *The authors contribute equally to this work.
This article reports novel roles and mechanisms of NADPH oxidase isoforms in mediating abdominal aortic aneurysm formation, through induction of eNOS uncoupling and vascular remodeling.
Zhang YX, Liu NM, Wang YC, Youn JY, Cai H. Endothelial cell calpain as a critical modulator of angiogenesis. (2017) BBA Mol. Basis of Disease. pii: S0925-4439(17)30108-4.
This article reviews novel signaling pathways and mechanisms underlying a critical role of endothelial cell calpain in the modulation of angiogenesis.
Zhang YX, Cai H. Endothelial to mesenchymal transition: When the good one goes bad. Editorial comments on “Endothelial to mesenchymal transition: A novel therapeutic target for cardiovascular diseases”. (2017) Trends in Cardiovasc Med.
This article is an editorial comment to discuss novel implications of endothelial to mesenchymal transition in the pathogenesis of cardiovascular diseases.
Liu NM, Siu KL, Youn JY, Cai H. Attenuation of neointimal formation with netrin-1 and netrin-1 preconditioned endothelial progenitor cells. J. Mol Med. 2017 95(3):335-348.
This article reports that chronic release of netrin-1 or injection of netrin-1 preconditioned endothelial progenitor cells (EPCs) remarkably attenuates neointimal formation and post-vascular endothelial injury. It indicates that netrin-1 and netrin-1 preconditioned EPCs can be used to effectively treat post-angioplasty coronary re-occlusion and restenosis, and points to a new way to manage the long-term complications of the angioplasty treatment of acute myocardial infarction.
Motivated and dedicated graduates with a PhD in Biomedical Sciences are welcome to apply for NIH-funded postdoctoral positions. Candidates with previous training and experiences in vascular biology, cardiac pathophysiology, molecular biology and/or free radical biology are preferred.
Graduate students via MCIP (Molecular, Cellular and Integrative Physiology), Molecular Pharmacology, and Molecular Biology Institute are welcome to apply for rotation positions.
Postdoctoral candidates please send CV, a brief description of previous training and research experiences, long-term career goals, representative publications in PDF, and three reference letters to Dr. Linda Cai ([email protected]).
The laboratory is also open to undergraduate researchers via the SPR program.