Novel Aortic Dissection Model Links Endothelial Dysfunction and Immune Infiltration

BACKGROUND: Aortic dissection (AD) is the separation of medial layers of the aorta and is a major cause of death in patients with connective tissue disorders such as Marfan syndrome. However, molecular triggers instigating AD, its temporospatial progression, and how vascular cells in each vessel layer interact and participate in the pathological process remain incompletely understood. To unravel the underlying molecular mechanisms of AD, we generated a spontaneous AD mouse model. METHODS: (fibrillin 1 Gly234Asp) protein to LTBPs (latent TGFβ transforming growth factor-beta binding proteins), and signaling pathways in the mutant aortic wall were examined by the Western blot analysis. RESULTS: lost the ability to bind to LTBP-1, -2, and -4, resulting in the downregulation of TGFβ signaling in the aortic wall. CONCLUSIONS: We show that interactions involving endothelial cells and macrophages/monocytes in the intima, where the extracellular matrix (ECM) microenvironment contains reduced TGFβ signaling, contribute to the initiation of AD. Our novel AD mouse model provides a unique opportunity to identify target molecules involved in the intimomedial tears that can be utilized for the development of therapeutic strategies.