Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HPMECs were successfully isolated by differential trypsinization from peripheral lung lobes. The cells proliferated rapidly in EGM-MV with 10% FBS and were serially cultivated for more than 20 passages (1:4 split ratio) in vitro. Cells were characterized as endothelial based upon their cobblestone morphology, the presence of factor VIII-related antigen, incorporation of DiI-Ac-LDL, tubule-like structure formation in Matrigel, and positive staining for ACE. Adhesion molecules were tested at passage 3 and passage 12. Cells demonstrated intense staining for PECAM-1 both unstimulated and stimulated with TNF-alpha (20 ng/ml). The adhesion molecules ICAM-1, VCAM-1, ELAM-1, and P-selectin differed in expression on unstimulated cells. ICAM-1 was constitutively expressed on unstimulated cells and the expression was increased by TNF-alpha stimulation (20 hr). In contrast, VCAM-1, ELAM-1, and P-selectin were not detected on unstimulated cells but were detected after stimulation with TNF-alpha. The inducibility of adhesion molecules was different. VCAM-1 (10 hr) and ELAM-1 (4 hr) were expressed more strongly than P-selectin (minutes to 4 hr). The adhesion molecule profile found on passage 12 was the same as on passage 3. CD36 was not detected on both unstimulated and stimulated (4 and 8 hr) cells. The peak of adhesion of HL-60 cells to TNF-alpha activated HPMEC monolayers was around 8 hr. The results indicate that HPMEC can be continuously grown in vitro for many passages without losing their adhesion molecule expression. This expression of adhesion molecules confirms that HPMECs might be a good in vitro model in the understanding of various aspects of pulmonary microvascular endothelial cell function and may be useful as the basis for studies of adhesion molecule targeted therapies of pulmonary inflammatory diseases.
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PMID:Expression of adhesion molecules in cultured human pulmonary microvascular endothelial cells. 858 50

Microvascular endothelial cells (MVEC), which differ from large vessel endothelial cells, have been isolated successfully from lungs of various species, including man. However, contamination by nonendothelial cells remains a major problem in spite of several technical improvements. In view of the organ specificity of MVEC, endothelial cells should be derived from the tissue involved in the diseases one wishes to study. Therefore, to investigate some of the immunopathological mechanisms leading to acute respiratory distress syndrome (ARDS), we have attempted to isolate lung MVEC from patients undergoing thoracic surgery for lung carcinoma and patients dying of ARDS. The method described here includes four main steps: (1) full digestion of pulmonary tissue with trypsin and collagenase, (2) aggregation of MVEC induced by human plasma, (3) Percoll density centrifugation, and (4) selection and transfer of MVEC after local digestion with trypsin/EDTA under light microscopy. Normal and ARDS-derived lung MVEC purified by this technique presented contact inhibition (i.e., grew in monolayer), and expressed classical endothelial markers, including von Willebrand factor (vWF), platelet endothelial cell adhesion molecule 1(PECAM-1, CD31), and transcripts for the angiotensin converting enzyme (ACE). The cells also formed capillarylike structures, took up high levels of acetylated low-density lipoprotein (Ac-LDL), and exhibited ELAM-1 inducibility in response to TNF. Contaminant cells, such as fibroblasts, smooth muscle cells, or pericytes, were easily recognized on the basis of morphology and were eliminated by selection of plasma-aggregated cells under light microscopy. The technique presented here allows one to study the specific involvement and contribution of pulmonary endothelium in various lung diseases.
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PMID:An improved method for isolation of microvascular endothelial cells from normal and inflamed human lung. 971 12

Atherosclerosis is still an important disease. It accounts for 39% of deaths in the U.K. and 12 million U.S citizens have atherosclerosis-associated disease. Atherosclerosis may exert clinical effects by slow narrowing, producing stable angina or dramatic rupture, producing acute coronary syndromes such as unstable angina or myocardial infarction and death. Macrophages are abundant in ruptured atherosclerotic plaques. Macrophages are innate immune effectors, i.e. they are activated without antigenic specificity. This may make them liable to indiscriminate tissue damage, since they are less selective than lymphocytes. Macrophages are recruited and activated by many signals and have an impressive armamentarium of molecules to promote tissue damage. Macrophage recruitment by abnormal endothelium over developing atherosclerotic plaques, is aided by endothelial expression of adhesion molecules (ICAM-1, VCAM, ELAM). Use of knockout mice has implicated the chemoattractant cytokine (chemokine) MCP-1 in attracting macrophage recruitment in atherosclerosis. Macrophage-activation stimuli associated with atherosclerotic risk factors include oxidised low density lipoprotein (oxLDL, "bad cholesterol"), advanced glycosylation end products (AGEs) of diabetes, angiotensin II and endothelin. Substantial work has clarified macrophage activation by OxLDL via macrophage scavenger receptors (MSRs), especially MSRA and CD36. Activated macrophages express effector molecules that kill cells and degrade extracellular matrix. These include Fas-L and nitric oxide (NO). Macrophage NO is derived from the high output inducible nitric oxide synthase (iNOS) pathway and upregulates vascular smooth muscle (VSMC) cell surface Fas, priming them for apoptosis. Activated macrophages express surface Fas-L, similar to cytotoxic T-lymphocytes and natural killer cells. Since VSMCs promote plaque stability, VSMC apoptosis may promote plaque rupture. Macrophages express multiple metalloproteinases (e.g. stromelysin) and serine proteases (e.g. urokinase) that degrade the extracellular matrix, weakening the plaque and making it rupture prone. Macrophages secrete numerous other effectors including reactive oxygen species, eicosanoids, tumour necrosis factor alpha and interleukin-1. Macrophage-derived transforming growth factor beta promotes fibrosis. Existing cardiovascular treatments including angiotensin II receptor antagonists and angiotensin converting enzyme inhibitors, aspirin, cholesterol reduction agents especially statins may inhibit macrophages. The interaction of NO-donors with macrophages and apoptosis is complex and bifunctional. Traditional anti-inflammatory agents such as glucocorticoids and cyclophosphamide have very serious side effects and are probably inappropriate. Novel anti-inflammatory agents e.g. new immunosuppressives and anti-TNF therapy may have an improved cost-benefit ratio.
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PMID:Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. 1563 83