Tags

Type your tag names separated by a space and hit enter

Tacrolimus limits polymorphonuclear leucocyte accumulation and protects against myocardial ischaemia- reperfusion injury.
J Mol Cell Cardiol. 2000 Mar; 32(3):429-40.JM

Abstract

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the pathogenesis of either human and experimental myocardial ischaemia. Tacrolimus, formerly known as FK506, has been previously shown to display cardioprotective effects on experimental ischaemia/reperfusion-induced myocardial damage. This study investigated whether cardioprotection induced by tacrolimus in myocardial ischaemia-reperfusion (MI/R) injury might be due to inhibition of the nuclear factor kappa B (NF- kappaB) that in turn causes reduced cardiac ICAM-1 expression and blunted polymorphonuclear leukocyte accumulation. Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5 h reperfusion (MI/R). Sham myocardial ischaemia-reperfusion rats (Sham MI/R) were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity, serum creatine kinase (CK) activity, cardiac mRNA for ICAM-1 reverse-transcriptase polymerase chain reaction, the inhibitory protein of NF- kappaB I kappaB alpha (Western blot analysis) in the myocardium-at-risk, and left ventricle d P/d t(max)were evaluated. Myocardial ischaemia plus reperfusion in untreated rats produced marked myocardial necrosis, increased serum CK activity and myeloperoxidase activity (MPO, a marker of leukocyte accumulation) both in the area at risk and in the necrotic area, and reduced the left ventricle dP/d t(max). Furthermore, inhibitory protein I kappaB alpha levels decreased, and cardiac mRNA for ICAM-1 increased, after 0.5 and 5 h of reperfusion, respectively. Administration of tacrolimus (25, 50 and 100microg/kg as an i.v. infusion 5 min after reperfusion) lowered myocardial necrosis and myeloperoxidase activity in the area at risk and in necrotic area, decreased serum CK activity, increased left ventricle dP/d t(max), reduced the loss the of inhibitory protein I kappaB alpha and blunted the message for ICAM-1. The present data suggest that tacrolimus blocks the early activation of the transcription factor NF- kappaB, suppresses ICAM-1 gene activation, reduces leukocyte accumulation and protects against myocardial ischaemia-reperfusion injury.

Authors+Show Affiliations

Institute of Pharmacology, University of Messina, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10731442

Citation

Squadrito, F, et al. "Tacrolimus Limits Polymorphonuclear Leucocyte Accumulation and Protects Against Myocardial Ischaemia- Reperfusion Injury." Journal of Molecular and Cellular Cardiology, vol. 32, no. 3, 2000, pp. 429-40.
Squadrito F, Altavilla D, Squadrito G, et al. Tacrolimus limits polymorphonuclear leucocyte accumulation and protects against myocardial ischaemia- reperfusion injury. J Mol Cell Cardiol. 2000;32(3):429-40.
Squadrito, F., Altavilla, D., Squadrito, G., Saitta, A., Deodato, B., Arlotta, M., Minutoli, L., Quartarone, C., Ferlito, M., & Caputi, A. P. (2000). Tacrolimus limits polymorphonuclear leucocyte accumulation and protects against myocardial ischaemia- reperfusion injury. Journal of Molecular and Cellular Cardiology, 32(3), 429-40.
Squadrito F, et al. Tacrolimus Limits Polymorphonuclear Leucocyte Accumulation and Protects Against Myocardial Ischaemia- Reperfusion Injury. J Mol Cell Cardiol. 2000;32(3):429-40. PubMed PMID: 10731442.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tacrolimus limits polymorphonuclear leucocyte accumulation and protects against myocardial ischaemia- reperfusion injury. AU - Squadrito,F, AU - Altavilla,D, AU - Squadrito,G, AU - Saitta,A, AU - Deodato,B, AU - Arlotta,M, AU - Minutoli,L, AU - Quartarone,C, AU - Ferlito,M, AU - Caputi,A P, PY - 2000/3/25/pubmed PY - 2000/6/10/medline PY - 2000/3/25/entrez SP - 429 EP - 40 JF - Journal of molecular and cellular cardiology JO - J Mol Cell Cardiol VL - 32 IS - 3 N2 - Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the pathogenesis of either human and experimental myocardial ischaemia. Tacrolimus, formerly known as FK506, has been previously shown to display cardioprotective effects on experimental ischaemia/reperfusion-induced myocardial damage. This study investigated whether cardioprotection induced by tacrolimus in myocardial ischaemia-reperfusion (MI/R) injury might be due to inhibition of the nuclear factor kappa B (NF- kappaB) that in turn causes reduced cardiac ICAM-1 expression and blunted polymorphonuclear leukocyte accumulation. Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5 h reperfusion (MI/R). Sham myocardial ischaemia-reperfusion rats (Sham MI/R) were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity, serum creatine kinase (CK) activity, cardiac mRNA for ICAM-1 reverse-transcriptase polymerase chain reaction, the inhibitory protein of NF- kappaB I kappaB alpha (Western blot analysis) in the myocardium-at-risk, and left ventricle d P/d t(max)were evaluated. Myocardial ischaemia plus reperfusion in untreated rats produced marked myocardial necrosis, increased serum CK activity and myeloperoxidase activity (MPO, a marker of leukocyte accumulation) both in the area at risk and in the necrotic area, and reduced the left ventricle dP/d t(max). Furthermore, inhibitory protein I kappaB alpha levels decreased, and cardiac mRNA for ICAM-1 increased, after 0.5 and 5 h of reperfusion, respectively. Administration of tacrolimus (25, 50 and 100microg/kg as an i.v. infusion 5 min after reperfusion) lowered myocardial necrosis and myeloperoxidase activity in the area at risk and in necrotic area, decreased serum CK activity, increased left ventricle dP/d t(max), reduced the loss the of inhibitory protein I kappaB alpha and blunted the message for ICAM-1. The present data suggest that tacrolimus blocks the early activation of the transcription factor NF- kappaB, suppresses ICAM-1 gene activation, reduces leukocyte accumulation and protects against myocardial ischaemia-reperfusion injury. SN - 0022-2828 UR - https://www.unboundmedicine.com/medline/citation/10731442/Tacrolimus_limits_polymorphonuclear_leucocyte_accumulation_and_protects_against_myocardial_ischaemia__reperfusion_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2828(99)91089-1 DB - PRIME DP - Unbound Medicine ER -