Abstract 20707: Macrophage Mitochondrial Fission is Essential for Continued Clearance of Apoptotic Cells and Plays a Protective Role in Advanced Atherosclerosis

Introduction: The mitochondrial dynamic processes of fission and fusion influence and integrate with multiple physiologic and pathophysiologic processes. Mitochondrial dynamics dysregulation has been implicated in atherosclerosis, but little is known about the role of myeloid cell specific mitochondrial dynamics in the progression of atherosclerosis. In macrophage-enriched murine atherosclerosis lesion areas, we have found that levels of mitochondrial fission protein DRP1 down-regulated as the lesion progresses. In contrast, the mitochondrial fusion protein MFN2 is up-regulated. Further, mitochondria in lesional macrophages show hyperfusion morphology as the lesion develops. These suggest that mitochondria in macrophages undergo hyperfusion during the lesion progression. Hypothesis: We hypothesize that mitochondrial hyperfusion plays a significant role in atherosclerosis. Methods: We used a model Drp1fl/fl LysmCre+/-Ldlr-/-mice who have hyperfused mitochondria in Mϕs to test the functional significance of...