# Study on the Role and Mechanism of TOPORS in Regulating Aortic Dissection by Mediating SUMOylation

## TL;DR

This study explores how TOPORS regulates aortic dissection through SUMOylation, showing that TOPORS promotes inflammation and cell death, worsening the condition.

## Contribution

The study reveals a novel role of TOPORS in aortic dissection via SUMOylation of p53, linking it to inflammation and cell apoptosis.

## Key findings

- TOPORS inhibition reduces aortic dilation and elastic fiber degradation in AD models.
- TOPORS suppression decreases inflammatory cytokines and promotes PI3K/AKT phosphorylation.
- TOPORS-mediated SUMOylation of p53 contributes to vascular smooth muscle cell apoptosis and AD progression.

## Abstract

Aortic dissection (AD) is a fatal acute cardiovascular emergency. SUMOylation participates in cell proliferation, apoptosis, and inflammation, but its role in AD, especially via TOPORS, remains unclear. This study investigates how TOPORS regulates AD pathogenesis through SUMOylation. AD and normal aortic samples were collected to detect TOPORS expression. AD mouse and VSMCs models were constructed to assess TOPORS depletion and overexpression effects on AD progression. In AD aortic tissues, TOPORS expression was upregulated, while tripartite motif containing 27 (TRIM27) and Sentrin-specific protease 6 (SENP6) expression showed no significant change. In vivo and in vitro experiments demonstrated that inhibition of TOPORS alleviated aortic dilation and elastic fiber degradation. TOPORS knockout suppressed the secretion of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IFN-α), promoted PI3K/AKT phosphorylation, and downregulated p53 signaling. The p53 inhibitor PFTα reduced AD-induced cell apoptosis and upregulation of inflammatory cytokines. Co-immunoprecipitation further confirmed that inhibition of TOPORS decreases SUMOylation of p53. Conclusions: TOPORS activates p53, inhibits PI3K/AKT phosphorylation via SUMOylation, promotes vascular smooth muscle cell (VSMC) apoptosis and inflammation, and exacerbates AD pathogenesis.