Objectives

CARDIORISK is a fully integrated programme which addresses both macrovascular (WP 3,5,7) and microvascular (WP4,5,6,7) radiation damage after local irradiation. Different groups will be using different experimental methods and models making use of the same cells and tissues most of which are centrally prepared and provided to all members of the research consortium. This way, results obtained in this research programme apply to identical biological material, treated identically with radiation.
Molecular and cellular responses at different times can thus be related directly to histopathological and functional changes of the irradiated microvasculature or the irradiated arteries.

CARDIORISK will perform in vivo and in vitro experimental studies to achieve the following objectives:

1. Elucidation of the pathogenic mechanisms of radiation-induced heart disease and of radiation-induced vascular damage after low and moderate radiation doses at the tissue, cell and molecular level (the primary objective of this project
2. Determination of the radiation dose dependence of the severity, latency, and rate of progression of cardiovascular radiation damage
3. Elucidation of the interaction between radiation-induced cardiovascular damage with other risk factors e.g. elevated cholesterol levels for atherosclerotic vascular damage and for microvascular damage.
4. Clarification of the histopathological and biochemical (proteomic) development of cardiovascular radiation damage, in particular elucidation of differences in responses at high ( =2 Gy such as in radiotherapy) and low radiation doses (=0.5 Gy as encountered in radiation protection).
5. Development of a dose specification system for inhomogeneous dose distribution in the heart and the cardiovascular system which will be based on the identification of critical subvolumes in the heart and their anatomical distribution in the organ.