Abstract

. The long-term goals of the applicants laboratory continue to be the elucidation of the properties and functions of pulmonary endothelial enzymes, in vivo, under normal and toxicant-altered environments. The goals of the current application focus on the applications of these functions in the development of clinically useful tests for the early diagnosis of lung injury. The studies performed since the initial award of this grant have provided new information and insights towards these long term goals. It is proposed to investigate mechanisms of angiotensin converting enzyme (ACE)-substrate and enzyme-inhibitor interactions in rabbit models of diabetes and microembolization, aiming to examine the induction as well as reversal and prevention of microvascular injury on enzyme function (diabetes) and also in studying mechanisms of altered perfused surface area (microembolization). In humans, it is proposed to investigate mechanisms of interaction between endothelium-bound ACE and clinically useful ACE inhibitors as well as correlate these interaction with the incidence of ACE gene polymorphism in an effort to identify target organ-specific ACE inhibitors and optimum biomarker conditions. Results of the proposed studies should help clarify mechanisms of induction, prevention and diagnosis of lung vascular injury.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL031422-13A1
Application #
2639838
Study Section
Special Emphasis Panel (ZRG4-ALTX-4 (01))
Project Start
1984-08-01
Project End
2002-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Medical College of Georgia (MCG)
Department
Biology
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912

  Publications

McCloud, Laryssa L; Parkerson, James B; Zou, Lihua et al. (2004) Reduced pulmonary endothelium-bound angiotensin converting enzyme activity in diabetic rabbits. Vascul Pharmacol 41:159-65
Orfanos, S E; Psevdi, E; Stratigis, N et al. (2001) Pulmonary capillary endothelial dysfunction in early systemic sclerosis. Arthritis Rheum 44:902-11
Orfanos, S E; Armaganidis, A; Glynos, C et al. (2000) Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in acute lung injury. Circulation 102:2011-8
Orfanos, S E; Parkerson, J B; Chen, X et al. (2000) Reduced lung endothelial angiotensin-converting enzyme activity in Watanabe hyperlipidemic rabbits in vivo. Am J Physiol Lung Cell Mol Physiol 278:L1280-8
Cziraki, A; Horvath, I; Rubin, J W et al. (2000) Quantification of pulmonary capillary endothelium-bound angiotensin converting enzyme inhibition in man. Gen Pharmacol 35:213-8
Orfanos, S E; Langleben, D; Khoury, J et al. (1999) Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in humans. Circulation 99:1593-9
Chen, X; Catravas, J D (1998) Release of a leukocyte activation inhibitor by staurosporine-treated pulmonary artery endothelial cells. Am J Physiol 275:L184-92
Horvath, I G; Cziraki, A; Parkerson, J B et al. (1998) Effect of acute coronary occlusion on the size of the dynamically perfused coronary capillary bed in the dog. Microvasc Res 56:95-103
Orfanos, S E; Ehrhart, I C; Barman, S et al. (1997) Endothelial ectoenzyme assays estimate perfused capillary surface area in the dog lung. Microvasc Res 54:145-55
Marczin, N; Antonov, A; Papapetropoulos, A et al. (1996) Monocyte-induced downregulation of nitric oxide synthase in cultured aortic endothelial cells. Arterioscler Thromb Vasc Biol 16:1095-103

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