Aortic dissection (AD) is a serious invasive vascular disease with an acute onset and high mortality rate. If not promptly intervened, the mortality rate increases by 1 %–2 % per hour within 48 h, and the mortality rate within 1 week is as high as 90 % [1]. Its severity is no less than cerebral hemorrhage and myocardial infarction, and it is one of the prevalent primary diseases that cause sudden death in clinical practice. Due to the diversity of clinical features of AD, clinical diagnosis and treatment are more difficult. Currently, there is no effective drug treatment. Surgical treatment is a more effective means to save patients' lives [2]. According to epidemiological investigations, the incidence of AD in women is much lower than in men, suggesting that estrogen may have a certain protective effect on the aorta [3]. The vascular protective effect of estrogen is mediated by estrogen receptors [4]. However, the mechanism of estrogen's effect on AD is still elusive. Current research indicates that genetic factors, hypertension, progressive degeneration of the aortic media, and aortic inflammation may be common pathogenic factors [5]. The structural and functional integrity of human arterial smooth muscle cells (HASMCs) is closely linked to the occurrence of AD and the progression of phenotypic switching [6]. Although many studies have attempted to elucidate the pathogenesis of AD, the potential molecular mechanisms behind its progression are still unclear, necessitating the exploration of effective preventive and therapeutic drugs. Therefore, it is particularly instrumental to explore the pathogenesis of AD and excavate its potential biomarkers or therapeutic targets at the molecular level for the clinical treatment of AD.

Small ubiquitin-related modifier (SUMO) modification is a type of post-translational modification of proteins that can modulate protein interactions, activity, and subcellular localization, thereby controlling various cellular processes [7]. SUMO molecules covalently bind to the lysine residues of substrate proteins through the participation of E1 activating enzymes, E2 conjugating enzymes, and E3 ligases, thereby modulating the structure and function of substrate proteins. This is a dynamic and reversible process [8]. SUMOylation predominantly depresses the activity of transcription factors, but as research deepens, SUMOylation is found to activate and stabilize some proteins [9]. SUMOylation has been proven to be linked to the pathogenesis of human diseases, such as cancer, cardiovascular disease, etc. [10]. For example, Qiu et al. [11] discovered that inflammation-induced high expression of SENP1 facilitates the de-SUMOylation of GATA2 in endothelial cells, thereby potentiating the protein stability of GATA2 and its binding ability to the promoters of related adhesion molecule genes, boosting endothelial activation and exacerbating the occurrence of atherosclerosis. SUMOylation is associated with regulating estrogen-estrogen receptor signaling. However, current relevant studies are limited to the field of cancer. In breast cancer (BC), ZFP282 can undergo SUMOylation, and the SUMO-modified ZFP282 enhances its binding to estrogen receptor α (ERα) and reinforces estrogen-mediated BC cell growth [12]. In summary, SUMOylation is crucial for the occurrence and development of human diseases. However, no reports dissect the regulatory function of SUMOylation in the progression of AD. A thorough exploration of its potential molecular mechanisms holds profound significance for elucidating the pathogenesis of AD and refining treatment status.

The E3 ubiquitin ligase tripartite motif (TRIM) family consists of more than 70 members, being essential in various cellular processes such as cell growth, differentiation, development, apoptosis, and inflammation [13]. The current study on TRIM family proteins focuses on their roles in anti-tumor therapy. Their dysregulated expression is closely linked to the occurrence and development of various cancers, and they have the potential to be biomarkers for cancer diagnosis and prognosis [14]. At the molecular mechanism level, the TRIM protein family exerts its effects by mediating ubiquitination modification of downstream related target proteins and controlling the stability of target proteins. For example, TRIM39, as a member of the TRIM family, can directly interact with PRDX3 and modulate renal fibrosis by ubiquitination modification of PRDX3 [15]. With the deepening of research, the TRIM protein family has been discovered to be SUMO E3 ligase and can connect SUMO molecules to substrates [16]. More TRIM family members have been found to function as SUMO E3 ligases, such as TRIM27, TRIM32, and TRIM36 [17]. Basu-Shrivastava M et al. [18] discovered that TRIM39 is a new SUMO E3 ligase that binds to NFATc3 and undergoes SUMOylation, thereby amplifying its stability and regulating neuronal apoptosis. However, the mechanism of SUMOylation of TRIM39 as a SUMOE3 ligase in AD has not been reported.

More effective therapeutic strategies of AD are required. TRIM39, a member of the TRIM protein family, exerts critical functions in multiple pathological contexts; however, its precise role and regulatory mechanisms in AD remain undefined. The present study aims to delineate the expression profile of TRIM39 in AD, elucidate its biological function—specifically its regulatory impact on the contractile phenotype of vascular smooth muscle cells—and dissect the underlying molecular mechanisms, including its potential involvement in ESR1 stability and the E2–ESR1 signaling axis. These efforts can clarify the potential of TRIM39 as a novel target for impeding AD progression and lay the groundwork for future TRIM39-directed therapeutic interventions.