RT Journal Article
T1 Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction
A1 Ramirez-Carracedo, Rafael
A1 Tesoro, Laura
A1 Hernández, Ignacio
A1 Diez-Mata, Javier
A1 Piñeiro, David
A1 Hernández Jiménez, Macarena
A1 Zaragoza, Carlos
A1 Zamorano Gómez, José Luis
AB 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).
PB MDPI
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/113569
UL https://hdl.handle.net/20.500.14352/113569
LA eng
NO Ramirez-Carracedo R, Tesoro L, Hernandez I, Diez-Mata J, Piñeiro D, Hernandez-Jimenez M, Zamorano JL, Zaragoza C. Targeting TLR4 with ApTOLL Improves Heart Function in Response to Coronary Ischemia Reperfusion in Pigs Undergoing Acute Myocardial Infarction. Biomolecules. 2020 Aug 9;10(8):1167. doi: 10.3390/biom10081167. PMID: 32784904; PMCID: PMC7464507.
NO Ministerio de Ciencia e Innovación (España) 
DS Docta Complutense
RD 21 ene 2026