Septic shock as a trigger of arterial stress-induced premature senescence: A new pathway involved in the post sepsis long-term cardiovascular complications - Archive ouverte HAL Access content directly
Journal Articles Vascular Pharmacology Year : 2021

Septic shock as a trigger of arterial stress-induced premature senescence: A new pathway involved in the post sepsis long-term cardiovascular complications

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Abstract

Background: Major adverse cardiovascular events among sepsis survivors is an emerging health issue. Because endothelial senescence leads to vascular dysfunction and atherothrombosis, sepsis could be associated to vascular stress-induced premature senescence and thus with long-term cardiovascular events. Materials & methods: Adult Wistar male rats were submitted to cecal ligation and puncture, or a SHAM operation. Markers of inflammation, oxidative stress and endothelial senescence were assessed at 3, 7 and 90 days (D), and vascular reactivity was assessed in conductance and resistance vessels at D90. Expression of proteins involved in senescence and inflammation was assessed by Western blot analysis and confocal microscopy, oxidative stress by dihydroethidium probing. Results: Pro-inflammatory endothelial ICAM-1 and VCAM-1 were up-regulated by three-fold in CLP vs. SHAM at D7 and remained elevated at D90. Oxidative stress followed a similar pattern but was detected in the whole vascular wall. Sepsis accelerated premature senescence in aorta vascular tissue as shown by the significant up-regulation of p53 and down-stream p21 and p16 senescent markers at D7, values peaking at D90 whereas the absence of significant variation in activated caspase-3 confirmed p53 as a prime inducer of senescence. In addition, p53 was mainly expressed in the endothelium. Sepsis-induced long-term vascular dysfunction was confirmed in aorta and main mesenteric artery, with a major alteration of the endothelial-dependent nitric oxide pathway. Conclusions: Septic shock-induced long-term vascular dysfunction is associated with endothelial and vascular senescence. Our model could prove useful for investigating senotherapies aiming at reducing long-term cardiovascular consequences of septic shock.
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hal-03364281 , version 1 (05-10-2022)

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Hamid Merdji, Mohamad Kassem, Louise Chomel, Raphaël Clere-Jehl, Julie Helms, et al.. Septic shock as a trigger of arterial stress-induced premature senescence: A new pathway involved in the post sepsis long-term cardiovascular complications. Vascular Pharmacology, 2021, pp.106922. ⟨10.1016/j.vph.2021.106922⟩. ⟨hal-03364281⟩
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