Endothelial and Macrophage-Specific Deficiency of P38α MAPK Does Not Affect the Pathogenesis of Atherosclerosis in ApoE-/- Mice

Background: The p38 alpha Mitogen-Activated Protein Kinase (MAPK) regulates stress-and inflammation-induced cellular responses. Factors implicated in the development of atherosclerosis including modified low-density lipoprotein (LDL), cytokines and even shear stress induce p38 activation in endothelial cells and macrophages, which may be important for plaque formation. This study investigates the effects of endothelial-and macrophage-specific deficiency of p38 alpha in atherosclerosis development, in Apolipoprotein E deficient (ApoE(-/-)) mice. Methodology/Principal Findings: ApoE(-/-) mice with macrophage or endothelial cell-specific p38 alpha deficiency were fed a high cholesterol diet (HCD) for 10 weeks and atherosclerosis development was assessed by histological and molecular methods. Surprisingly, although p38 alpha-deficiency strongly attenuated oxidized LDL-induced expression of molecules responsible for monocyte recruitment in endothelial cell cultures in vitro, endothelial-specific p38 alpha ablation in vivo did not affect atherosclerosis development. Similarly, macrophage specific deletion of p38 alpha did not affect atherosclerotic plaque development in ApoE(-/-) mice. Conclusions: Although previous studies implicated p38 alpha signaling in atherosclerosis, our in vivo experiments suggest that p38 alpha function in endothelial cells and macrophages does not play an important role in atherosclerotic plaque formation in ApoE deficient mice.