Trehalose attenuates abdominal aortic aneurysm formation by inducing autophagy in smooth muscle cells

Bo Jiang; Xuan Li; Mo Wang; Guang-Xin Li; Peng-Wei Ren; Yu-Qi Wang; Shi-Jie Xin; Ling-Feng Qin

doi:10.26599/1671-5411.2023.03.002

Trehalose attenuates abdominal aortic aneurysm formation by inducing autophagy in smooth muscle cells

J Geriatr Cardiol. 2023 Mar 28;20(3):214-222. doi: 10.26599/1671-5411.2023.03.002.

Authors

Bo Jiang¹, Xuan Li¹, Mo Wang², Guang-Xin Li³, Peng-Wei Ren², Yu-Qi Wang^{4

5}, Shi-Jie Xin¹, Ling-Feng Qin²

Affiliations

¹ Department of Vascular Surgery, the First Hospital of China Medical University, Key Laboratory of Pathogenesis, Prevention and Therapeutics of Aortic Aneurysm, Shenyang, China.
² Department of Surgery, Yale School of Medicine, New Haven, CT, USA.
³ Department of Breast and Thyroid Surgery, Peking University Shenzhen Hospital, Shenzhen, China.
⁴ Yale Stem Cell Center, Yale School of Medicine, New Haven, CT, USA.
⁵ Department of Biomedical Engineering, Yale University, New Haven, CT, USA.

Abstract

Background: Trehalose is a naturally occurring disaccharide, which has been identified as an autophagy inducer and exhibits protective effect in cardiovascular diseases such as myocardial infraction and atherosclerosis. However, the functional role of trehalose in abdominal aortic aneurysm (AAA) remains undefined.

Methods: To study the effect of trehalose in AAA, trehalose (1 g/kg per day) were given for 14 continuous days in a mouse model of elastase-induced abdominal aortic aneurysm. On day 14, ultrasound was performed to measure aortic diameter before the abdominal aortas were harvested and processed for further analysis. Verhoeff-Van Gieson staining and TUNEL staining were performed on paraffin sections to evaluate vascular histology and apoptosis, immunofluorescence staining and Western-blot were performed to evaluate expression of autophagy markers.

Results: Echocardiography and in situ pictures demonstrated that trehalose attenuated infrarenal aorta dilation. Verhoeff-Van Gieson staining showed elastin degradation was improved in trehalose-treated group. Compared with vehicle-treated mice, trehalose treatment restored smooth muscle cell contractile phenotype with increased α-SMA, Calponin and Myh11 expression. Furthermore, trehalose also attenuated cell apoptosis and leukocytes infiltration. Importantly, trehalose induced autophagy with decrease SQSTM1/p62 accumulation, increased lamp2 expression and LC3B conversion.

Conclusion: Trehalose attenuated AAA progression with decreased inflammation and restored SMC contractile phenotype by inducing autophagy. These results demonstrated the therapeutic potential of trehalose in AAA.