Inflammatory Mechanisms Contributing to Aortic Expansion and Rupture after Acute Aortic Dissection

Abstract

In-hospital outcomes are generally acceptable with the conservative treatment of uncomplicated type B aortic dissection, but some patients present with undesirable complications, such as aortic expansion and rupture. Beyond mechanical and shear forces of blood flow affecting the weakened aortic wall, excessive inflammatory response has been shown to be associated with aortic expansion and adverse clinical outcomes. We have previously demonstrated the underlying mechanisms of catastrophic complications after acute aortic dissection (AAD) in mice. We propose that aortic dissection induces expression of the neutrophil chemoattractants CXCL1 and granulocyte-colony stimulating factor in the aortic tunica adventitia. These local environmental changes recruit neutrophils in combination with alteration of bone marrow milieu where reduced CXCL12 expression enhances neutrophil egress. Interleukin (IL)-6 production in the inflammatory adventitial neutrophils causes vascular inflammation, leading to vascular wall fragility. Targeting CXCR2 or IL-6 mitigates aortic expansion and prevents mice from aortic rupture. Collectively, adventitial neutrophil-mediated inflammation may be a potential therapeutic target to limit lethal complications after AAD.