The role and potential mechanism of deoxycorticosterone acetate plus salt-induced aneurysm development
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1.Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS); Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, National Health Commission, Beijing 100021, China. 2.Beijing Engineering Research Center for Laboratory Animal Models of Human Critical Diseases, Beijing 100021. 3. Ningxia Medical University, Yinchuan 750004

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R-33

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    Abstract:

    Objective To investigate the induction of abdominal aortic aneurysm by DOCA plus high salt at different time points and the undeRLying molecular mechanism. Methods Ten-month-old C57BL/ 6J mice were divided into two groups: a high-salt group (HS) and a DOCA plus high-salt group (DOCA+HS). Each group received the designated treatments for 1 week, 2 weeks, and 3 weeks. At the end of treatment, the mice were anesthetized with isoflurane followed by ultrasonography and aorta collection to observe abdominal aorta expansion and aneurysm formation. H&E staining, Masson’ s staining, and elastic fiber staining were performed to detect pathological changes, collagen deposition, and elastic fiber fragmentation, respectively. Immunohistochemistry was used to detect abdominal aortic inflammatory cell infiltration, and RT-PCR was used to detect the mRNA expression of inflammatory and anti-inflammatory factors. RNA sequencing was conducted to analyze the differentially-expressed genes and the enrichment signaling pathways of these genes in the arterial tissues of the two groups of mice after 3 weeks of treatment. Results Compared with the HS group, DOCA+ HS treatment for 1 week did not induce the formation of abdominal aortic aneurysms in mice, but after 2 weeks of treatment, the mice began to form aortic aneurysms. The incidence of aortic aneurysm was 44% at week 2 and 65% at week 3. With increased duration of DOCA+HS treatment, collagen deposition in the abdominal aorta increased, and elastic fiber fragmentation was observed. Meanwhile, high inflammatory cell infiltration (mainly macrophages and T cells) was observed in the abdominal aorta of mice after treatment with DOCA+HS for 2 weeks and 3 weeks. The mRNA levels of inflammatory factors increased significantly, while the mRNA levels of anti-inflammatory factors decreased. Additional transcriptome sequencing result showed that the differentially-expressed genes in the two groups of mice after 3 weeks of treatment were enriched mainly in the immune system and metabolic pathways, and that levels of the key molecule PSGL-1, which mediates leukocyte adhesion, increased significantly after 3 weeks of DOCA+ HS treatment. Conclusions DOCA+ HS treatment can induce abdominal aortic aneurysm formation in mice after 2 weeks of therapy. PSGL-1 and its mediated inflammation may play important roles.

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History
  • Received:October 09,2020
  • Revised:
  • Adopted:
  • Online: March 02,2021
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