ASP is considered to be critical for triglyceride synthesis and the maintenance of metabolic homeostasis, although the importance of C3adesArg in systemic lipid metabolism remains controversial and has been contradicted in previous studies. Hematological parameters were not changed throughout the course of this study. While circulating factor D inhibits thrombin-induced platelet aggregation in vitro there was no effect of properdin deficiency on platelet number or activation at any time point. In terms of atherosclerotic plaque burden, properdin was protective in male mice but only when fed a LFD. This concurs with the study by Persson who also found that positive effects of C3 deletion were overwhelmed at later time points, 26 weeks in that specific study. The authors linked the early phenotype to the possible presence of neutrophils in lesions and since properdin is produced by neutrophils this could also play a role in our study. This early effect of properdin on lesions points to a potential role in ‘mild’ rather than ‘moderate’ or ‘complex’ lesion formation. In our study, there was no increase in VSMC whose excessive proliferation as part of the stereotypic atherosclerotic process causes thickened vessel walls and accumulation in plaques. Only the % of macrophages in lesions and their phenotype appeared altered by properdin deletion, with enhanced lipid storage function and increased expression of CD206, MCP-1 and arginase, supporting a likely M2 phenotype. In keeping with suggestions from Bacci and Fujisaka et al. that M2 macrophages are over recruited under conditions of a high fat diet especially when metabolic disturbance e.g. insulin resistance and weight gain occurs, we find the greatest Oil red O lesion areas, indicative of foam cells, in HFD fed female and male mice. In conclusion, this definitive study indicates that the positive regulator of the alternative complement pathway has antiatherogenic effects in an unstressed situation. This effect appears restricted to male mice only and is overwhelmed by feeding a HFD. We postulate that normal levels of C3 and the presence of properdin appear to be protective in experimental atherosclerosis. Properdin has a unique role in the complement system and further studies directed at more metabolic aspects of atherosclerosis may be valuable. There is frequently a requirement to use non-aqueous solvents in biological experiments, for example, to dissolve pharmacological agents that have a limited aqueous solubility. This manipulation is usually performed by making a concentrated stock solution in 100% solvent that is subsequently diluted into aqueous media to generate a final solution for application to the cells, tissue or organism under investigation. Good experimental design dictates that the drug-treated group is then compared to a group treated with only the vehicle TH-302 in vivo containing solution. What is less frequently considered, however, is what effects do the vehicle containing solutions produce in their own right.