All-trans retinoic acid attenuates the progression of Ang II-induced abdominal aortic aneurysms in ApoE\u2212/\u2212mice

Jie Xiao,Jinping Liu,Iohang Lio,Chuanlei Yang,Xing Chen,Hua Zhang,Shuxia Wang,Zhanjie Wei

doi:10.1186/s13019-020-01208-w

Abstract

BackgroundTo determine whether all-trans retinoic acid (ATRA) can influence the development of Angiotensin II (Ang II) induced experimental abdominal aortic aneurysms (AAAs).MethodsApolipoprotein E knock-out (ApoE−/−) mice were randomly assigned to 4 groups. Mice in the AAA and ATRA groups underwent continuous subcutaneous Ang II infusion for 28 days to induce AAA, while the Sham and Control groups were infused with saline. Systolic blood pressure was measured by the tail-cuff technique. The Control and ATRA groups received ATRA treatment. Aortic tissue samples were obtained at 28 days after surgery and evaluated by aortic diameter measurement, Western blotting, immunohistochemistry, and hematoxylin-eosin (H&E) and Verhoeff-Van Gieson (EVG) staining.ResultsThe abdominal aortic diameter was significantly reduced in the ATRA group compared with the AAA group (3 of 12 (25%) vs 9 of 12 (75%), P < 0.05), and the ATRA group exhibited reduced blood pressure on days 7, 14, and 28. Low expression of angiotensin II receptor type 1 (AT1), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) and EVG staining revealed a significant reduction in the disruption of elastic fibers in the abdominal aortic tissue of the ATRA group compared to the AAA group. Western blot analysis indicated that protein levels of retinoic acid receptor α (RARα), MMP2, MMP9, and AT1 were dramatically affected by ATRA treatment.ConclusionsIn conclusion, ATRA attenuates the progression of Ang II-induced AAAs, possibly by downregulating MMP2, MMP9, and AT-1 expression.

Highlights

To determine whether all-trans retinoic acid (ATRA) can influence the development of Angiotensin II (Ang II) induced experimental abdominal aortic aneurysms (AAAs)
The mice were randomly assigned to 4 groups: Sham group, Control group, AAA group (Ang II infusion + corn oil, 0.1 ml, orally administration daily after surgery, n = 12), and ATRA group (Ang II infusion + ATRA-corn oil suspension, 0.1 ml, 3 days prior to surgery and orally administration daily after surgery, n = 12)
Angiotensin II induces AAAs in ApoE−/− mice, and treatment with ATRA reduces AAA incidence and mortality rate Three mice died from aortic dissection (AD) in the AAA group (3 of 12, 25%) one died from AD in the ATRA group (1 of 12, 8.3%), and no mice died in the Sham or Control groups during the 28-day experiment

Summary

Introduction

To determine whether all-trans retinoic acid (ATRA) can influence the development of Angiotensin II (Ang II) induced experimental abdominal aortic aneurysms (AAAs). Mice in the AAA and ATRA groups underwent continuous subcutaneous Ang II infusion for 28 days to induce AAA, while the Sham and Control groups were infused with saline. The global mortality due to abdominal aortic aneurysms (AAAs) is high, and AAAs are believed to be associated with age-related degenerative disease. Diverse pathogenicity factors have been described in AAA, including smoking, high blood pressure, and obesity. These risk factors are similar to those for atherosclerosis, and the intimal pathology of atherosclerosis and thrombosis are similar to that of AAA [7]

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