Areas of Interest
We are investigating the production of extravascular tissue
plasminogen activator (t-PA) by sympathetic neurons, and its
effects on the blood and vessel wall fibrinolysis. Plasmin,
formed by the action of t-PA on plasminogen, is the master
enzyme of fibrinolysis and extracellular matrix remodeling.
Extravascular plasmin produced by t-PA is able to degrade most
proteins, and is a principal activator of latent
metalloproteinases that also degrade the matrix. In various
immunological reactions, plasmin is a principal activator of
important cytokines, such as TGF-b which regulates numerous
immune and healing reactions. As such plasmin production plays a
major role in the pathogenesis of vessel wall diseases, e.g.,
hypertension, atherosclerosis and thromboembolism.
Within most tissues and organs the vascular endothelial cell
is thought to be the principal source of tissue plasminogen
activator. Our studies have confirmed that greater amounts of
the protease are synthesized, transported and released by
sympathetic nerve cells that innervate the vessel walls and
other extracellular matrices throughout the body. This indicates
that t-PA is distributed by the sympathetic nervous system to
multiple tissues and organs. The implications of this neural
fibrinolysis for diseases of ageing are studied in appropriate
animal models using invitro t-PA release measurements in organ
cultures and morphologic TEM studies of t-PA distribution.
Publications
Selected Publications
Wang, Y. Ghalil, W. Pingle, P., Traboulsi, A. Dalal, T.
O'Rourke, J. and Cone, R.E. Splenic cells from mice receiving
intracameral antigen suppress in vitro antigen‑induced
proliferation and interferon‑g production by sensitized lymph
node cells. Ocular Immunol and Inflam., (In press).
Jiang, X., Hand, A.R., Shen, S., Cone, R.E. and O'Rourke, J.
Enhanced tissue plasminogen activator synthesis by the
sympathetic neurons that innervate aging vessels. J. Neurosci
Res. 71:567‑594, 2003.
Wang, Y., Jiang, X., Hand, A.R., Gillies, C., Kirk, J., Gone,
R.E., and O'Rourke, J. Additional evidence that the sympathetic
nervous system regulates the vessel wall release of tissue
plasminogen activator. Blood Coag. and Fibrinolysis 13:1‑11,
2002.
Jiang, X., Wang, Y., Hand, A_R., Gillies, C., Cone, R.E.
Kirk, J., and O'Rourke, J. Storage and release of tissue
plasminogen activator (t‑PA) by sympathetic axons in resistance
vessel walls. Microvascular Research 64:438‑447, 2002.
Wang, Y., Goldschneider, I., O'Rourke, J. and Cone, R.E.
Blood mononuclear cells induce regulatory NK T lymphocytes in
anterior chamber‑associated immune deviation. J. Leukocyte Biol.
69:741‑746, 2001.
Jiang, X, Wang, Y., Hand, A.R., Gillies, C., and O'Rourke, J.
Presence of tissue plasminogen activator (t‑PA) in the
adventitial sympathetic nerves that innervate small arteries:
Morphologic evidence for a neural fibrinolysis. Fibrinolysis and
Proteolysis 14:35‑46, 2000.
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