Gut Microbiota-Derived Tryptophan Metabolite Indole-3-aldehyde Ameliorates Aortic Dissection

Abstract

Tryptophan, an essential dietary amino acid, is metabolized into various metabolites within both gut microbiota and tissue cells. These metabolites have demonstrated potential associations with panvascular diseases. However, the specific relationship between tryptophan metabolism, particularly Indole-3-aldehyde (3-IAId), and the occurrence of aortic dissection (AD) remains unclear. 3-IAId showed an inverse association with advanced atherosclerosis, a risk factor for AD. In this study, we employed a well-established β-aminopropionitrile monofumarate (BAPN)-induced AD murine model to investigate the impact of 3-IAId treatment on the progression of AD. Our results reveal compelling evidence that the administration of 3-IAId significantly mitigated aortic dissection and rupture rates (BAPN + 3-IAId vs. BAPN, 45% vs. 90%) and led to a notable reduction in mortality rates (BAPN + 3-IAId vs. BAPN, 20% vs. 55%). Furthermore, our study elucidates that 3-IAId exerts its beneficial effects by inhibiting the phenotype transition of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic state. It also mitigates extracellular matrix degradation, attenuates macrophage infiltration, and suppresses the expression of inflammatory cytokines, collectively contributing to the attenuation of AD development. Our findings underscore the potential of 3-IAId as a promising intervention strategy for the prevention of thoracic aortic dissection, thus providing valuable insights into the realm of vascular disease management.