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

@article{citeulike:5923028, abstract = {10.1073/pnas.0908924106 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 \^{A}± 9.47 mmHg compared to 59.3 \^{A}± 7.8 mmHg in wild-type MSCs and 37.8 \^{A}± 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 \^{A}± 1.76\% versus wild-type MSCs (57.4 \^{A}± 1.33\%) and vehicle (39.2 \^{A}± 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 \^{A}± 2.16\% compared to 46.4 \^{A}± 1.92\% in wild-type MSCs and 60.7 \^{A}± 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.}, author = {Wang, Meijing and Tan, Jiangning and Wang, Yue and Meldrum, Kirstan K. and Dinarello, Charles A. and Meldrum, Daniel R.}, citeulike-article-id = {5923028}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0908924106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/41/17499.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/41/17499.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19805173}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19805173}, day = {13}, doi = {10.1073/pnas.0908924106}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {il-18, il18-review}, month = {October}, number = {41}, pages = {17499--17504}, posted-at = {2009-10-12 00:45:32}, priority = {2}, title = {IL-18 binding protein-expressing mesenchymal stem cells improve myocardial protection after ischemia or infarction}, url = {http://dx.doi.org/10.1073/pnas.0908924106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:5923028 L3 - citeulike-article-id:5923028 N2 - 10.1073/pnas.0908924106 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 ± 9.47 mmHg compared to 59.3 ± 7.8 mmHg in wild-type MSCs and 37.8 ± 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 ± 1.76% versus wild-type MSCs (57.4 ± 1.33%) and vehicle (39.2 ± 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 ± 2.16% compared to 46.4 ± 1.92% in wild-type MSCs and 60.7 ± 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. IS - 41 JF - Proceedings of the National Academy of Sciences SN - 1091-6490 EP - 17504 TI - IL-18 binding protein-expressing mesenchymal stem cells improve myocardial protection after ischemia or infarction VL - 106 SP - 17499 KW - il-18 KW - il18-review AU - Wang, Meijing AU - Tan, Jiangning AU - Wang, Yue AU - Meldrum, Kirstan AU - Dinarello, Charles AU - Meldrum, Daniel PY - 2009/10/13/ UR - http://dx.doi.org/10.1073/pnas.0908924106 ER -