UPON RETURNING HOME FROM SPACE FLIGHT THE CARDIOVASCULAR SYSTEM OF ASTRONAUTS IS ALTERED WITH CHANGES MANIFESTING IN WHAT IS TERMED CARDIOVASCULAR DECONDITIONING. ESSENTIALLY THIS MEANS THAT THEIR CARDIOVASCULAR SYSTEM IS NOT FUNCTIONING PROPERLY. IT IS WELL KNOWN THAT PROPER FUNCTION OF THE CARDIOVASCULAR SYSTEM IS LARGELY DEPENDENT ON THE MAINTENANCE OF HEALTHY FUNCTIONING VASCULAR CELLS NAMELY ENDOTHELIAL CELLS THAT LINE BLOOD VESSELS SMOOTH MUSCLE CELLS WHICH MAKE UP THE UNDERLYING VESSEL WALL AND A POPULATION OF "REPAIR" CELLS TERMED ENDOTHELIAL STEM/PROGENITOR CELLS FOUND IN CIRCULATING BLOOD. WORK HAS SHOWN THAT ENDOTHELIAL CELLS ARE EFFECTED BY MICROGRAVITY CONDITIONS. IN FACT IN A GROUNDBREAKING STUDY PROVIDED THROUGH GENELAB ENDOTHELIAL CELLS WERE STUDIED UNDER CONDITIONS OF SPACE FLIGHT. THE STUDY TERMED SPACEFLIGHT OF HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS (SPHINX) WAS PART OF THE PROGRESS 40P SPACE MISSION WHICH LASTED FOR 10 DAYS. THE RESULTS OBTAINED FROM GENELAB ON THE SPACE STUDY AS WELL AS PUBLISHED REPORTS SHOW THAT IN RESPONSE TO REAL MICROGRAVITY AS SEEN IN SPACE ENDOTHELIAL CELLS BECOME ALTERED AND DYSFUNCTIONAL. THIS STUDY EVALUATED VIA MICROARRAY TECHNOLOGY GENE EXPRESSION CHANGES THAT GOVERN A MYRIAD OF FUNCTIONAL PROCESSES. IT IS OUR HYPOTHESIS THAT THESE CHANGES IN ENDOTHELIAL CELLS WILL SIGNIFICANTLY ALTER IMPORTANT CELL-CELL COMMUNICATIONS BETWEEN ENDOTHELIAL CELLS AND SMOOTH MUSCLE CELLS AS WELL AS ENDOTHELIAL CELLS AND CIRCULATING PROGENITOR CELLS. GIVEN THE CRITICAL NATURE OF THESE CELL-CELL INTERACTIONS IN MAINTAINING VESSEL HOMEOSTASIS IT IS IMPORTANT THAT WE UNDERSTAND THE EFFECT OF MICROGRAVITY ON THIS CROSS TALK AND CORRELATE OUR FINDINGS WITH THE GENE AND PROTEIN EXPRESSION CHANGES IN ENDOTHELIAL CELLS AS SHOWN IN THE SPHINX STUDY. THIS PROPOSAL SEEKS TO STUDY CO-CULTURED ENDOTHELIAL AND SMOOTH MUSCLE CELLS UNDER MODELLED MICROGRAVITY TO ASSESS CHANGES IN SMOOTH MUSCLE CELL PROCESSES SUCH AS PROLIFERATION AND CONTRACTION. SIMILARLY WE SEEK TO STUDY CO-CULTURED ENDOTHELIAL CELLS AND CIRCULATING STEM/PROGENITOR CELLS UNDER CONDITIONS OF MODELLED MICROGRAVITY TO ASSESS CHANGES IN THE STEM CELLS DIFFERENTIATION AND ANTI-THROMBOGENIC FUNCTION. WE ALSO WILL ASSESS FUNCTIONAL CHANGES IN THE ENDOTHELIAL CELLS THEMSELVES TO CORRELATE THE GENETIC CHANGES WITH ANTI-THROMBOGENIC RESPONSES. THE WORK PROPOSED IS INSPIRED BY THE GENELAB DATA FROM THE SHPINX STUDY THAT REVEALED IMPORTANT GENETIC CHANGES IN ENDOTHELIAL CELLS. WE HOPE TO EXPAND ON THIS DATA BY REVEALING IMPORTANT FUNCTIONAL BEHAVIORS OF ENDOTHELIAL CELLS TOWARDS THE GOAL OF THE DEVELOPMENT OF CELL BASED COUNTERMEASURES TO ADDRESS THE CHALLENGES OF CARDIOVASCULAR DECONDITIONING.