Hypoxia suppresses stretch-induced elongation and orientation of macrophages

BACKGROUND: Cells in the arterial wall are normally subjected to approximately 10% cyclic stretch due to pulsatile blood flow. In addition, cells in the walls of abdominal aortic aneurysms (AAA) experience hypoxic conditions caused by the accumulation of intraluminal thrombus. Such combined stimulation by hypoxia and stretch can induce abnormal functions in macrophages that infiltrate into the AAA walls; however, the details of these effects are unknown. OBJECTIVE: The aim of this study is to know the influence of a combination of cyclic stretch and hypoxia on the macrophage morphology. METHODS: Morphological changes, such as aspect ratio and orientation, in macrophages exposed to 10% cyclic stretch and 2.2% O₂ hypoxia during 24 h were evaluated with usage of ImageJ software. We also assessed expression of hypoxia-inducible factor-α (HIF-1α), an intracellular signaling factor, in macrophages by western blotting. RESULTS: The results indicate that hypoxia significantly suppresses stretch-induced orientation in the direction of the stretch and elongation of macrophages. We also found that the combination of cyclic stretch and hypoxia significantly increased HIF-1α expression. CONCLUSIONS: These results suggest that hypoxia suppresses morphological responses of macrophages to cyclic stretch by elevating HIF-1α expression.