A Calcium Phosphate-Induced Mouse Abdominal Aortic Aneurysm Model

Summary

This protocol describes a calcium phosphate-induced abdominal aortic aneurysm (AAA) mouse model to study the pathological features and molecular mechanisms of AAAs.

Abstract

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease that occurs worldwide and is characterized by irreversible dilation of the abdominal aorta. Currently, several chemically induced murine AAA models are used, each simulating a different aspect of the pathogenesis of AAA. The calcium phosphate-induced AAA model is a rapid and cost-effective model compared to the angiotensin II- and elastase-induced AAA models. The application of CaPO₄ crystals to the mouse aorta results in elastic fiber degradation, loss of smooth muscle cells, inflammation, and calcium deposition associated with aortic dilation. This article introduces a standard protocol for the CaPO₄-induced AAA model. The protocol includes material preparation, the surgical application of the CaPO₄ to the adventitia of the infrarenal abdominal aorta, the harvesting of aortas to visualize aortic aneurysms, and histological analyses in mice.

Introduction

An abdominal aortic aneurysm (AAA) is a lethal cardiovascular disease characterized by permanent dilation of the abdominal aorta, with high mortality rates once rupture occurs. AAA is associated with aging, smoking, male gender, hypertension, and hyperlipidemia¹. Several pathological processes have been shown to contribute to AAA formation, including extracellular matrix fiber proteolysis, immune cell infiltration, and loss of vascular smooth muscle cells. Currently, the pathological mechanisms of AAA remain elusive, and there are no proven drugs for the treatment of AAA¹. Research into human AAA is limited due to the ex....

Protocol

Animal studies were performed in compliance with the guidelines of the Institutional Animal Care and Use Committee of Peking University Health Science Center and were approved by the Biomedical Ethics Committee of Peking University (LA2015142). All the mice for surgery were anesthetized with isoflurane (1.5%-2%), and anesthesia was carefully monitored to avoid pain or discomfort for the mice.

1. Preparation

1. Cut 0.3 cm wide strips of powder-free rubber gloves and ga.......

Discussion

Periaortic application of CaPO₄ is a robust approach to induce AAA in mice. Several studies have used the CaPO₄ model and consistently reported that this is a rapid and reproducible method to study AAA in mice^7,9. This model is considered to recapitulate part of the features of human aortic aneurysm and provide mechanistic insights into AAA pathogenesis, including inflammation and extracellular matrix degradation.

Materials

Name	Company	Catalog Number	Comments
CaCl2	MECKLIN	C805225
NaCl	Biomed	SH5001-01
PBS	HARVEYBIO	MB5051
Small animal ventilator	RWD	H1550501-012