Acid sphingomyelinase/ceramide mediates structural remodeling of cerebral artery and small mesenteric artery in simulated weightless rats

Abstract

AimsWeightlessness 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. Main methodsRats 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. Key findingsDuring 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. SignificanceThe 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.