Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toll-like receptor 4 (TLR4) contributes to the pathogenesis of coronary ischemia/reperfusion (IR). To test whether the new TLR4 antagonist, ApTOLL, may prevent coronary IR damage, we administered 0.078 mg/kg ApTOLL or Placebo in pigs subjected to IR, analyzing the levels of cardiac troponins, matrix metalloproteinases, pro-, and anti-inflammatory cytokines, heart function, and tissue integrity over a period of 7 days after IR. Our results show that ApTOLL reduced cardiac troponin-1 24 h after administration, improving heart function, as detected by a significant recovery of the left ventricle ejection fraction (LVEF) and the shortening fraction (FS) cardiac parameters. The extension of necrotic and fibrotic areas was also reduced, as detected by Evans blue/2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxylin/Eosine, and Masson Trichrome staining of heart sections, together with a significant reduction in the expression of the extracellular matrix-degrading, matrix metalloproteinase 9. Finally, the expression of the following cytokines, CCL1, CCL2, MIP1-A-B, CCL5, CD40L, C5/C5A, CXCL1, CXCL10, CXCL11, CXCL12, G-CSF, GM-CSF, ICAM-1, INF-g, IL1-a, ILI-b, IL-1Ra, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, IL16, IL17-A, IL17- E, IL18, IL21, IL27, IL32, MIF, SERPIN-E1, TNF-a, and TREM-1, were also assayed, detecting a pronounced decrease of pro-inflammatory cytokines after 7 days of treatment with ApTOLL. Altogether, our results show that ApTOLL is a promising new tool for the treatment of acute myocardial infarction (AMI).
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PMID:Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction. 3278 4

Acute myocardial infarction (AMI) is one of the leading causes of death and disability. The dysregulation of cardiac endothelial cells plays a significant role in the pathogenesis of AMI. In the present study, we investigated the potential of memantine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist used in the treatment of Alzheimer's disease, to mitigate the effects of ischemia-reperfusion injury in the peripheral vasculature using human umbilical cord endothelial cells (HUVECs). Previous studies have identified anti-inflammatory and antioxidant effects of memantine, but the effects of memantine on angiogenesis and microtubule formation have not been fully elucidated. Our findings indicate that pretreatment with memantine significantly reduced the expression of interleukin (IL)-6 and IL-8, which are both serum markers if AMI severity. We also demonstrate that memantine could prevent mitochondrial dysfunction and oxidative stress by rescuing mitochondrial membrane potential and reducing the production of reactive oxygen species (ROS) by NADPH oxidase-4 (NOX-4). Importantly, memantine also promoted the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant signaling pathway. Importantly, memantine pretreatment improved cell viability and prevented the decrease in microtubule formation induced by OGD/R. Through a phosphoinositide-3-kinase (PI3K) inhibition experiment, we determined that the PI3K/protein kinase B (Akt) pathway is essential for the effects of memantine on angiogenesis. Together, our findings suggest a potential role for memantine in the prevention and treatment of AMI.
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PMID:The protective effects of memantine against inflammation and impairment of endothelial tube formation induced by oxygen-glucose deprivation/reperfusion. 3317 67


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