109 ERYTHROPOIETIN TREATMENT INHIBITED NADPH OXIDASE-DERIVED SUPEROXIDE PRODUCTION AND ENDOTHELIAL DYSFUNCTION IN NITRIC OXIDE SYNTHASE INHIBITOR-TREATED RAT AORTA
Bibliographic record
Abstract
Objectives: We and other researchers reported that nitric oxide (NO) plays an important role in pleiotropic tissue-protective effects of erythropoietin (ISH 2010, Vancouver). This study was aimed to investigate the other mechanisms of erythropoietin-induced vasoprotection using NO synthase inhibitor-treated rats. Design and methods: Erythropoietin (75 U/kg, s.c.) was administered to NO synthase inhibitor (L-NAME, 0.7 mg/ml in drinking water)-treated rats for 2 weeks. Systolic blood pressure (SBP) and hematocrit was measured, and aorta was excised for the following investigations. Acetylcholine-induced relaxation was determined. Cryosections were prepared to detect macrophages and osteopontin by immunohistochemistry and to stain with hematoxylin-eosin. Immunoblotting was performed to assay the phospho-Akt, heme oxygenase-1 (HO-1), Cu/Zn-superoxide dismutase (SOD) and suppressor of cytokine signaling 1 (SOCS1) proteins. NADPH oxidase was measured by a luminescence assay. In addition, erythropoietin was administered to angiotensinII-treated cultured vascular endothelial cells with/without STAT5 inhibitor. Results: There was no significant difference in hematocrit among all groups. Erythropoietin had no effect on the increased SBP in L-NAME-treated rats. Erythropoietin improved endothelium-dependent vasodilatation. Macrophage infiltration, overexpression of osteopontin, and hyperplasia in L-NAME-treated rats were reduced by erythropoietin. Erythropoietin enhanced the levels of phospho-Akt, HO-1 and Cu/Zn-SOD protein. The increased NADPH oxidase activity in L-NAME-treated rat was suppressed by erythropoietin. Erythropoietin also induced SOCS1 overexpression. Cotreatment with STAT5 inhibitor canceled erythropoietin-induced suppression in NADPH oxidase activation in angiotensinII-treated endothelial cells.Conclusions: Erythropoietin inhibited vascular injury in L-NAME-treated rats by increasing antioxidant enzymes. In addition, erythropoietin suppressed NADPH oxidase-derived superoxide production by increasing SOCS1 expression. References: Simopoulos AP, Cleland LG, editors. Omega-6/Omega-3 Essential Fatty Acid Ratio: The Scientific Evidence in World Rev Nutr Diet, Basel, Karger, 2003: 92:1-22. Na S, Collin O, Chowddury F, Tay B, Ouyang M, Wang Y, Wang N. Rapid signal transduction in living cells is a unique feature of mechanotransduction. Proc Natl Acad Sci USA 2008; 105: 186626-186631. Hoffman BD, Grashoff C, Schwartz MA. Dynamic molecular processes mediate cellular mechanotransduction. Nature 2011; 475(7356): 316-323.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".