Weightlessness exposure conduces to substantial vascular remodeling, mechanisms behind which remain unclear. Acid sphingomyelinase (ASM) catalyzed ceramide (Cer) generation accounts for multiple vascular disorders, so the role of it in adjustment of cerebral artery (CA) and small mesenteric artery (MA) was investigated in simulated weightless rats. Rats were hindlimb unloaded tail suspended (HU) to simulate the effect of weightlessness. Arterial morphology was examined by hematoxylin-eosin staining. Cer abundance was measured by immunohistochemistry. Western blotting was used to detect protein content. Apoptosis was detected by transferase-mediated dUTP nick end labeling. During 4 weeks of tail suspension, intima-media thickness (IMT) and media cross section area (CSA) were increased gradually in CA but decreased gradually in MA (P < 0.05). Correspondingly, the apoptosis and proliferation of vascular smooth muscle cells were reduced and enhanced respectively in CA (P < 0.05), while promoted and restrained in MA (P < 0.05). As compared to control, both ASM protein expression and Cer content were lowered in CA and elevated in MA of HU rats (P < 0.05). Permeable Cer incubation reversed the change of apoptosis and proliferation in CA of HU rats, while ASM inhibition recapitulated it in control rats. On the contrary, ASM inhibitors restored the alteration of apoptosis and proliferation in MA of HU. The results suggest that by controlling the balance between apoptosis and proliferation, ASM/Cer exerts an important role in structural adaptation of CA and MA to simulated weightlessness.

中文翻译：

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酸性鞘磷脂酶/神经酰胺介导模拟失重大鼠脑动脉和肠系膜小动脉的结构重塑


失重暴露会导致大量的血管重塑，其背后的机制仍不清楚。酸性鞘磷脂酶（ASM）催化神经酰胺（Cer）的生成是多种血管疾病的原因，因此在模拟失重大鼠中研究了其在调节脑动脉（CA）和肠系膜小动脉（MA）中的作用。对大鼠进行后肢卸载尾悬（HU）以模拟失重效果。通过苏木精-伊红染色检查动脉形态。通过免疫组织化学测量 Cer 丰度。 Western blotting用于检测蛋白质含量。通过转移酶介导的 dUTP 缺口末端标记检测细胞凋亡。悬尾4周期间，CA中的内膜中层厚度（IMT）和中膜横截面积（CSA）逐渐增加，而MA中逐渐减少（P％3C<0.05）。相应地，血管平滑肌细胞的凋亡和增殖在CA中分别减少和增强(P<<0.05)，而在MA中则促进和抑制(P<<0.05)。与对照组相比，HU大鼠CA中ASM蛋白表达和Cer含量均降低，而MA中ASM蛋白表达和Cer含量升高（P<<0.05）。可渗透性 Cer 孵育逆转了 HU 大鼠 CA 中细胞凋亡和增殖的变化，而 ASM 抑制则在对照大鼠中重现了这一变化。相反，ASM抑制剂恢复了HU的MA细胞凋亡和增殖的改变。结果表明，通过控制细胞凋亡和增殖之间的平衡，ASM/Cer 在 CA 和 MA 对模拟失重的结构适应中发挥重要作用。