Project Details
Projekt
Molecular Imaging of Myocardial Inflammation and the Progression of Heart Failure
Applicant
Professor James Thackeray, Ph.D.
Subject Area
Nuclear Medicine, Radiotherapy, Radiobiology
Term
from 2016 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 319331954
In a heart attack, heart muscle cells can become damaged. This injury results in inflammation, the leaking of immune cells into the heart tissue from the blood. White blood cells participate in the healing process by removing dead and damaged cells. They also produce chemical signals to attract bone marrow stem cells which contribute to healing after injury. Inflammation in the healing process is a delicate balance. Too much can result in damage to otherwise healthy tissue. Too little can result in build-up of dead cells and unstable scar, leading to rupture. The degree of inflammation may be predictive of healing or development of heart failure. It may also affect the attraction and retention of regenerative stem cells from the bone marrow. We aim to develop a non-invasive imaging platform to measure inflammation and predict progression of heart failure. Mice will be given a heart attack by typing off a blood vessel in the heart. The amount of inflammation will be controlled by drugs to block or limit the leaking of immune cells into the damaged tissue. Radioactive probes that bind to inflammatory cells will be injected. The signal from these probes can be detected using a PET camera. This provides a non-invasive measurement of inflammation in the heart. We will measure the inflammation over time to show:a) how specific drugs affect early stage inflammationb) whether the degree of inflammation affects progression of heart failured) whether reducing inflammation improves heart function We will then assess how early inflammation affects reparative cell recruitment. Mouse bone marrow will be modified to include a reporter gene (HSVtk) on their surface. These cells are transplanted into mice that have their natural bone marrow removed. These bone marrow cells can be tracked by giving a radioactive probe that sticks to HSVtk and a PET camera. This provides a map of stem cells in the body. We will then measure the movement of stem cells. Mice with HSVtk bone marrow will be given a heart attack or pressure-overload. We will measure the radioactive signal in the heart over time to determine how many cells move to the injury and how long they remain. a) How many stem cells home to the injured tissue after initial damage b) How long the stem cells stay in the injured area c) Whether stem cell attraction and retention is affected by inflammation Understanding the progression of heart disease and natural repair processes can help to develop new treatments to promote healing. Genetic changes to stem cells may improve cell therapy, and allow a timed activation of the treatment. The imaging markers of inflammation are already used in hospitals and clinics. By learning the relationship between early inflammation, stem cell homing and heart failure, we can better stratify patient risk and optimize treatment.
DFG Programme
Research Grants
