Myocardial ischemia reperfusion injury, a consequence of organ preservation and implantation, adversely impacts both early and late outcomes after heart transplantation. As heart failure is highly prevalent among the veteran population, this area of investigation is of very high significance. While neutrophils are critical mediators of myocardial ischemia reperfusion injury, little is known about their trafficking and activation requirements during this form of sterile inflammation. Utilizing our newly developed technique of intravital imaging of beating mouse hearts, we have uncovered a role for innate immune molecules in donor hearts for entry of neutrophils into the graft tissue of freshly reperfused cardiac transplants. This application proposes to study mechanisms for neutrophil recruitment during myocardial ischemia reperfusion injury of heart grafts and will allow for the development of new therapeutic strategies.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01BX002730-05
Application #
10039494
Study Section
Cardiovascular Studies A (CARA)
Project Start
2015-10-01
Project End
2020-09-30
Budget Start
2019-10-01
Budget End
2020-09-30
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
St. Louis VA Medical Center
Department
Type
DUNS #
033986766
City
St. Louis
State
MO
Country
United States
Zip Code
63106
Li, Wenjun; Luehmann, Hannah P; Hsiao, Hsi-Min et al. (2018) Visualization of Monocytic Cells in Regressing Atherosclerotic Plaques by Intravital 2-Photon and Positron Emission Tomography-Based Imaging-Brief Report. Arterioscler Thromb Vasc Biol 38:1030-1036
Hsiao, Hsi-Min; Fernandez, Ramiro; Tanaka, Satona et al. (2018) Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1?. J Clin Invest 128:2833-2847
Takahashi, T; Hsiao, H M; Tanaka, S et al. (2018) PD-1 expression on CD8+ T cells regulates their differentiation within lung allografts and is critical for tolerance induction. Am J Transplant 18:216-225
Li, Wenjun; Hsiao, Hsi-Min; Higashikubo, Ryuji et al. (2016) Heart-resident CCR2+ macrophages promote neutrophil extravasation through TLR9/MyD88/CXCL5 signaling. JCI Insight 1:
Liu, Y; Li, W; Luehmann, H P et al. (2016) Noninvasive Imaging of CCR2+ Cells in Ischemia-Reperfusion Injury After Lung Transplantation. Am J Transplant 16:3016-3023