Background and Aims:
To evaluate number, viability and function of circulating endothelial progenitor cells (EPCs) with role in the pathogenesis of aortic valve disease, particularly in diabetic mice with atherosclerosis.

Methods:
A diabetic ApoE-/- mouse model was used to identify early and progressive changes, at 4 or 7 days after the last streptozotocin or citrate buffer injection, when diet was switched from standard chow to atherogenic diet. Blood and aortic valves from treated or non-treated ApoE-/- and C57BL/6 animals were collected. EPCs were identified by CD34 and VEGFR2 staining and the expression of a4b1, aVb3, aVb5, b1, a5 integrins and CXCR4 chemokine receptor on EPC surface were assessed by flow cytometry. EPC recruitment in aortic valve was measured by fluorescence microscopy of CD34+ cells in valve sections.

Results
Atherogenic diet induced EPC apoptosis, regardless of the presence of diabetes, as shown by significant higher caspase-3 levels. However, at both tested time points, diabetic mice had significantly lower blood EPC levels than the corresponding non-diabetic animals. EPCs from diabetic mice expressed α4β1 and αVβ3 integrins at a lower level, the rest of integrins and CXCR4 being seemingly unaffected by diabetes or diet. Aortic valves from mice fed 7 days with atherogenic diet presented a significantly higher number of EPCs recruited and diabetes abolished EPC recruitment at this time point.

Conclusions:
Reduced EPC number and expression of α4β1 and αVβ3 integrins on EPCs at 4 and 7 days after diabetes induction in atherosclerosis-prone mice resulted in lower recruitment of EPCs in the aortic valve.

06 - EARLY DIABETES INDUCES ALTERATIONS IN ENDOTHELIAL PROGENITOR CELL PHENOTYPE AND HOMING IN MICE SUSCEPTIBLE TO ATHEROSCLEROSIS