The purpose of this project is to improve the clinical usefulness of serum angiotensin converting enzyme (SACE) determinations in the diagnosis and treatment of patients with sarcoidosis and other granulomatous diseases by defining serum and tissue angiotensin converting enzyme (ACE) heterogeneity. Definition of SACE heterogeneity would ultimately allow routine clinical laboratory testing for ACE isoenzymes, analogous to present creatinine kinase (CK) and lactic dehydrogenase (LD) isoenzyme determinations. Although ACE heterogeneity has been defined in animals, the following questions concerning human ACE remain to be answered and will be addressed by this project: 1. Does total human SACE reflect organ specific contributions or only an endothelial cell component? Do these contributions vary in sarcoidosis and other granulomatous diseases? 2. What proportion of enzymatic human SACE is active immunologically? Does this specific activity vary in sarcoidosis and other granulomatous diseases? The methodology will focus on the biochemical characterization of human ACE in both the serum and tissues of normals and patients with disease by: Molecular weights, isoelectric point, enzymatic activity, immunlogic activity, carbohydrate content, effect of carbohydrate cleavage, effect of various inhibitors on activity. This project has a high likelihood of success since it reflects a straight-forward biochemical approach to the determination of human ACE heterogeneity using proven methods from successful animal and human research.
| Tahmoush, Albert J; Amir, Mary S; Connor, William W et al. (2002) CSF-ACE activity in probable CNS neurosarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 19:191-7 |
| Munoz, S J; Patrick, H; Moritz, M (1993) Heterogeneous effect of liver transplantation on the granuloma-enhancing factor of primary biliary cirrhosis. Transplant Proc 25:1927-9 |
