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Critical Role of Dendritic Cells in Wound healing after Myocardial Infarction in CD11c‐DTR‐GFP Mice
Author(s) -
Pruthi Dafina,
De Muinck Ebo,
Fu Qiangwei,
McGarr Robert,
Moodie Karen
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb72
Subject(s) - cd11c , angiogenesis , diphtheria toxin , cardiac function curve , genetically modified mouse , wound healing , medicine , myocardial infarction , transgene , ejection fraction , cardiology , endocrinology , biology , immunology , phenotype , toxin , heart failure , gene , biochemistry
Dendritic Cells (DC) are known primarily for their function as antigen presenting cells. Recently it has been shown that DC acquire an endothelial phenotype and contribute significantly to tumor angiogenesis and were named vascular leukocytes (VLC). Our laboratory has shown in mice that VLC appear as early as one day after MI in the healing heart and that they reach their peak at day 7 in infarcted area which coincides with the peak of angiogenesis in this model. We asked if early depletion of DC which are the precursors of VLC, would result in changes in wound healing. Methods We investigated cardiac wound healing in CD11c‐DTR‐GFP transgenic mice at day 7 after inducing MI with and without depletion of CD11c DC (transgenic mouse has a transgene encoding simian Diphtheria toxin receptor under control of murine CD11c promoter, allows to specifically deplete CD11c DC by injecting Diphtheria toxin (DT)). Mice were randomized to injection with 8ng/g i.p. of DT just before MI surgery or PBS. We measured functional cardiac recovery (%ejection fraction‐ EF%) with echocardiography; cardiac diastolic and systolic function with pressure volume loops system (PV‐loops); morphometry to assess myocardial necrosis on the TTC stained slices. Results Echocardiography: average EF% at day 7 for mice with intact DC and depleted DC is 27% and 49% respectively, n=16, p=0.001. Morphometry: MI% at day 7, 57% and 19.4% respectively, n=16, p=0.001. PV loops: Cardiac Output (uL/min) at day 7, 7826 and 3161, End‐diastolic Pressure (mmHg) at day 7, 9.4 and 17.1 Conclusion CD11c+ DCs play a significant and previously unrecognized role in post‐MI wound healing with DC depletion after MI resulting in a significant reduction of myocardial necrosis and a significantly better functional recovery of the heart.