Cardiac Critical Care Research Program
Summary
Science
Features
To investigate the role of cardiac and bone-marrow-derived TLR4 signaling in ischemic injury and to define the cellular and molecular mechanisms that govern such processes, we employ several mouse models of ischemic myocardial injury and a variety of biochemistry, molecular biology, and physiology techniques as described below.
TOLL-LIKE RECEPTOR 4 (TLR4) SIGNALING PATHWAYS
MOUSE MODELS OF ISCHEMIC CARDIAC INJURY
In vivo: Thoracotomy and coronary artery ligation
Ex vivo: Langendorff model in isolated hearts
In vitro: Hypoxic cardiomyocyte cultures
GENETIC MANIPULATION
| Knock-out mice: |
TLR4-/-, TLR2-/-, MyD88-/-, IRAK-1-/-, iNOS-/- |
| Adenovirus (Ad)-mediated transgene expression: |
Ad.MyD88-wt, Ad.MyD88-dn, Ad.IRAK-1-wt,
Ad.IRAK-1-kd (kinase-deficient) |
| Chimeric models: |
KO -> WT, WT -> KO
(Donor -> Recipient bone marrow transplantation)
|
CARDIAC FUNCTION ASSESSMENT
END POINTS
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