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Biomedical subjects

E Napoleone

Publications and source records attributed to E Napoleone.

5 recordsLinked to original sources
PubMed2000

Angiotensin-converting enzyme inhibitors downregulate tissue factor synthesis in monocytes.

Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of recurrent myocardial infarction in patients with left ventricular dysfunction. Tissue factor (TF), the initiator of blood coagulation, plays a pivotal role in arterial thrombosis that occurs after atherosclerotic plaque fissuring. Because monocytes synthesize TF and contain several components of the renin-angiotensin system, we investigated the possibility that ACE inhibitors could modulate monocyte TF expression. Mononuclear leukocytes from healthy volunteers were incubated with endotoxin in the presence or absence of different ACE inhibitors. Captopril reduced TF expression in endotoxin-stimulated mononuclear leukocytes, as measured by a 1-stage clotting assay and ELISA analysis, by approximately 60%. The effect was dose-dependent and was attributable to ACE inhibition, given that other ACE inhibitors, such as idrapril or fosinopril, and losartan, an antagonist of the angiotensin II AT(1) receptor, caused a comparable reduction in TF activity. Reverse transcriptase-polymerase chain reaction indicated that endotoxin-mediated increased levels of TF mRNA were inhibited by ACE inhibitors. Moreover, endotoxin-induced nuclear factor-kappaB translocation to the promoter region of the gene encoding for TF was markedly inhibited by captopril. The finding that ACE inhibitors and angiotensin II AT(1) antagonists can potentially modulate TF expression by mononuclear cells has important biological and therapeutic implications for the evolution of thrombi. Our results suggest that the anti-ischemic effect of these drugs might be explained, at least in part, by their ability to reduce TF expression in monocytes.

Angiotensin Receptor Antagonists↗
PubMed1998

Cell-cell interaction and tissue factor expression.

Following tissue injury, blood components come into contact with the subendothelial tissue, a thrombogenic surface. Tissue factor, found in the media and adventitia of the vascular wall, or available on the membrane of activated monocytes and endothelial cells, triggers blood coagulation. A complex interaction between soluble molecules and cells then takes place, a fibrin mesh is formed, and the resulting clot limits or stops the loss of blood. Platelets, monocytes, and endothelial cells co-localize and interact in the area of vascular injury. This close relationship, which is regulated by an array of cell-cell adhesion molecules, favours the modulation of the biochemical pathways of these cells. The aim of this review is to summarize the contribution of these cells and their interactions in tissue factor expression and its possible relevance in the pathogenesis of vascular diseases.

Blood Platelets↗
PubMed1997

Monocytes upregulate endothelial cell expression of tissue factor: a role for cell-cell contact and cross-talk.

Monocytes and endothelial cells interact at sites of vascular injury during inflammatory response, thrombosis, and development of atherosclerotic lesions. Such interactions result in modulation of several biological functions of the two cell types. Because both cells, on appropriate stimulation, synthesize tissue factor (TF), we examined the effect of human umbilical vein endothelial cell (HUVEC)/monocyte coculture on the expression of TF. We found that the coincubation resulted in TF generation, which was maximal at 4 hours, increased with increasing numbers of monocytes, and required mRNA and protein synthesis. Supernatant from HUVEC/monocyte coculture induced TF activity in HUVECs, but not in monocytes, indicating that HUVEC were the cells responsible for the activity, and that soluble mediators were involved. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), well-known inducers of TF in HUVECs, were found in the supernatant from the coculture, and specific antibodies directed against either cytokine inhibited TF generation. The need of IL-1 beta and TNF-alpha synthesis in order to elicit TF expression was also suggested by the delay observed in TF mRNA formation and TF activity generation when monocytes were incubated with HUVECs. IL-1 beta and TNF-alpha antigen levels in the coculture supernatant, and, consequently, HUVEC TF expression, were inhibited in the presence of anti-CD18 monoclonal antibody. These findings emphasize the role of cell-cell contact and cross-talk in the procoagulant activity, which could be responsible for the thromboembolic complications observed in those vascular disorders in which monocyte infiltration is a common feature.

Cell Communication↗
PubMed1989

Anti-goat immunoglobulin antibodies in diabetic children at diagnosis and follow-up: comparison with islet cell antibodies and other autoantibodies.

The presence of antibodies reacting with human as well as animal immunoglobulins in sera from recent onset Type I diabetic patients has been recently demonstrated by some of our group. In the present study, the occurrence of these antibodies has been evaluated in sera from 19 Type I diabetic patients, at diagnosis and at follow-up within three years, and from 26 normal subjects, and has also been compared with the presence of islet cell antibodies and other organ-specific autoantibodies. A solid-phase radioimmunoassay has been used: serum was incubated in goat immunoglobulin-coated wells and the binding of 125-I-anti-human immunoglobulin antibodies was evaluated. Anti-goat immunoglobulin antibodies were above the 90th percentile of normal values in all diabetic patients at diagnosis (median, interquartile range, in micrograms 125I-antibody bound/1 serum: 83, 77.5-88, versus 51.5, 44.5-62 in normal subjects, P less than 0.001) and significantly declined with time after diagnosis (P less than 0.001). Islet cell antibodies were present in 79% of patients at diagnosis, whereas at least one other auto-antibody was found in 21% of patients. In the follow-up study the decline in anti-goat immunoglobulin antibody levels was different from that of islet cell antibody positivity. A circulating immunoglobulin reacting with other immunoglobulins is thus present in the early stages of Type I diabetes and may well play a part in the complex immunopathogenetic interactions.

Animals↗