Affiliation:
1. Department of General & Vascular Surgery Xiangya Hospital Central South University Changsha Hunan China
2. Department of Physiology Nanjing Medical University Nanjing Jiangsu China
3. Department of Surgery Stanford University School of Medicine Stanford CA
4. National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha Hunan China
Abstract
Background
The protective effects of polyamines on cardiovascular disease have been demonstrated in many studies. However, the roles of spermidine, a natural polyamine, in abdominal aortic aneurysm (
AAA
) disease have not been studied. In this study, we investigated the influence and potential mechanisms of spermidine treatment on experimental
AAA
disease.
Methods and Results
Experimental
AAA
s were induced in 8‐ to 10‐week‐old male C57
BL
/6J mice by transient intra‐aortic infusion of porcine pancreatic elastase. Spermidine was administered via drinking water at a concentration of 3 mmol/L. Spermidine treatment prevented experimental
AAA
formation with preservation of medial elastin and smooth muscle cells. In immunostaining, macrophages, T cells, neutrophils, and neovessels were significantly reduced in aorta of spermidine‐treated, as compared with vehicle‐treated elastase‐infused mice. Additionally, flow cytometric analysis showed that spermidine treatment reduced aortic leukocyte infiltration and circulating inflammatory cells. Furthermore, we demonstrated that spermidine treatment promoted autophagy‐related proteins in experimental
AAA
s using Western blot analysis, immunostaining, and transmission electron microscopic examination. Autophagic function was evaluated for human abdominal aneurysmal and nonaneurysmal adjacent aortae from
AAA
patients using Western blot analysis and immunohistochemistry. Dysregulated autophagic function, as evidenced by increased
SQSTM
1/p62 protein and phosphorylated
mTOR
, was found in aneurysmal, as compared with nonaneurysmal, aortic segments.
Conclusions
Our results suggest that spermidine supplementation limits experimental
AAA
formation associated with preserved aortic structural integrity, attenuated aortic inflammatory infiltration, reduced circulating inflammatory monocytes, and increased autophagy‐related proteins. These findings suggest that spermidine may be a promising treatment for
AAA
disease.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
20 articles.
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