RGD Reference Report - IL-18 binding protein-expressing mesenchymal stem cells improve myocardial protection after ischemia or infarction. - Rat Genome Database

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IL-18 binding protein-expressing mesenchymal stem cells improve myocardial protection after ischemia or infarction.

Authors: Wang, M  Tan, J  Wang, Y  Meldrum, KK  Dinarello, CA  Meldrum, DR 
Citation: Wang M, etal., Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17499-504. Epub 2009 Sep 25.
RGD ID: 4889400
Pubmed: PMID:19805173   (View Abstract at PubMed)
PMCID: PMC2752405   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0908924106   (Journal Full-text)

IL-18 is a proinflammatory cytokine known to cause tissue injury by inducing inflammation and cell death. Increased levels of IL-18 are associated with myocardial injury after ischemia or infarction. IL-18-binding protein (IL-18BP), the naturally occurring inhibitor of IL-18 activity, decreases the severity of inflammation in response to injury. In the present study, mesenchymal stem cells (MSCs) derived from mice transgenic for over expression of human IL-18BP were tested in rat models of global myocardial ischemia and acute myocardial infarction. Improved myocardial function is associated with production of VEGF, and in vitro, IL-18BP MSCs secreted higher levels of constitutive VEGF compared to wild-type MSCs. Whereas IL-18 increased cell death and reduced VEGF in wild-type MSCs, IL-18BP MSCs were protected. In an isolated heart model, intracoronary infusion of IL-18BP MSCs before ischemia increased postischemic left ventricular (LV) developed pressure to 79.5 + or - 9.47 mmHg compared to 59.3 + or - 7.8 mmHg in wild-type MSCs and 37.8 + or - 5 mmHg in the vehicle group. Similarly, using a coronary artery ligation model, intramyocardial injection of IL-18BP MSCs improved LV ejection fraction to 67.8 + or - 1.76% versus wild-type MSCs (57.4 + or - 1.33%) and vehicle (39.2 + or - 2.07%), increased LV fractional shortening 1.25-fold over wild-type MSCs and 1.95-fold over vehicle, decreased infarct size to 38.8 + or - 2.16% compared to 46.4 + or - 1.92% in wild-type MSCs and 60.7 + or - 2.2% in vehicle, reduced adverse ventricular remodeling, increased myocardial VEGF production, and decreased IL-6 levels. This study provides the concept that IL-18BP genetically modified stem cells improve cardioprotection over that observed with unmodified stem cells.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  

Objects Annotated

Genes (Rattus norvegicus)
Il18  (interleukin 18)
Il18bp  (interleukin 18 binding protein)

Genes (Mus musculus)
Il18  (interleukin 18)
Il18bp  (interleukin 18 binding protein)

Genes (Homo sapiens)
IL18  (interleukin 18)
IL18BP  (interleukin 18 binding protein)


Additional Information