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Rapamycin Treatment Attenuates Angiotensin II -induced Abdominal Aortic Aneurysm Formation via VSMC Phenotypic Modulation and Down-regulation of ERK1/2 Activity

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Abstract

The aim of the present study is to address the effect of rapamycin on abdominal aortic aneurysm (AAA) and the potential mechanisms. A clinically relevant AAA model was induced in apolipoprotein E-deficient (ApoE-/-) mice, in which miniosmotic pump was implanted subcutaneously to deliver angiotensin II (Ang II) for 14 days. Male ApoE-/- mice were randomly divided into 3 groups: saline infusion, Ang II infusion, and Ang II infusion plus intraperitoneal injection of rapamycin. The diameter of the supra-renal abdominal aorta was measured by ultrasonography at the end of the infusion. Then aortic tissue was excised and examined by Western blotting and histoimmunochemistry. Ang n with or without rapamycin treatment was applied to the cultured vascular smooth muscle cells (VSMCs) in vitro. The results revealed that rapamycin treatment significantly attenuated the incidence of Ang II induced-AAA in ApoE-/- mice. Histologic analysis showed that rapamycin treatment decreased disarray of elastin fibers and VSMCs hyperplasia in the medial layer. Immunochemistry staining and Western blotting documented the increased phospho-ERK1/2 and ERK1/2 expression in aortic walls in Ang II induced-AAA, as well as in human lesions. Whereas in the rapamycintreated group, decreased phospho-ERKl/2 expression level was detected. Moreover, rapamycin reversed Ang II -induced VSMCs phenotypic change both in vivo and in vitro. Based on those results, we confirmed that rapamycin therapy suppressed Ang II -induced AAA formation in mice, partially via VSMCs phenotypic modulation and down-regulation of ERK1/2 activity.

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Author notes

  1. Both authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Fei-fei Li  (李飞飞), Xiao-ke Shang  (尚小珂), Xin-ling Du  (杜心灵) & Shu Chen  (陈 澍)

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  1. Fei-fei Li  (李飞飞)
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  2. Xiao-ke Shang  (尚小珂)
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  3. Xin-ling Du  (杜心灵)
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  4. Shu Chen  (陈 澍)
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Corresponding author

Correspondence to Shu Chen  (陈 澍).

Additional information

This project was supported by grants from the National Natural Science Foundation of China (No. 81570325), and the Fundamental Research Funds for the Central Universities.

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Li, Ff., Shang, Xk., Du, Xl. et al. Rapamycin Treatment Attenuates Angiotensin II -induced Abdominal Aortic Aneurysm Formation via VSMC Phenotypic Modulation and Down-regulation of ERK1/2 Activity. CURR MED SCI 38, 93–100 (2018). https://doi.org/10.1007/s11596-018-1851-z

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  • DOI: https://doi.org/10.1007/s11596-018-1851-z

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