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Abstract：
Marfan syndrome (MFS) is a rare congenital disorder of the connective tissue, leading to thoracic aortic aneurysms (TAA) and dissection, among other complications. Currently, the most efficient strategy to prevent life-threatening dissection is preventive surgery. Periodic imaging applying complex techniques is required to monitor TAA progression and to guide the timing of surgical intervention. Thus, there is an acute demand for non-invasive biomarkers for diagnosis and prognosis, as well as for innovative therapeutic targets of MFS. Unraveling the intricate pathomolecular mechanisms underlying the syndrome is vital to address these needs. High-throughput platforms are particularly well-suited for this purpose, as they enable the integration of different datasets, such as transcriptomic and epigenetic profiles. In this narrative review, we summarize relevant studies investigating changes in both the coding and non-coding transcriptome and epigenome in MFS-induced TAA. The collective findings highlight the implicated pathways, such as TGF-β signaling, extracellular matrix structure, inflammation, and mitochondrial dysfunction. Potential candidates as biomarkers, such as miR-200c, as well as therapeutic targets emerged, like Tfam, associated with mitochondrial respiration, or miR-632, stimulating endothelial-to-mesenchymal transition. While these discoveries are promising, rigorous and extensive validation in large patient cohorts is indispensable to confirm their clinical relevance and therapeutic potential.
摘要：
马凡氏综合征（MFS）是一种罕见的先天性结缔组织疾病，导致胸主动脉瘤（TAA）和夹层，在其他并发症中。目前,预防危及生命的夹层最有效的策略是预防性手术.需要应用复杂技术的周期性成像来监测TAA进展并指导手术干预的时机。因此，对用于诊断和预后的非侵入性生物标志物的需求非常迫切，以及MFS的创新治疗目标。解开综合征背后的复杂病理分子机制对于满足这些需求至关重要。高通量平台特别适合此目的，因为它们能够集成不同的数据集，如转录组和表观遗传谱。在这篇叙述性评论中，我们总结了研究MFS诱导的TAA中编码和非编码转录组和表观基因组变化的相关研究。集体发现突出了牵连的途径，如TGF-β信号，细胞外基质结构，炎症,和线粒体功能障碍。作为生物标志物的潜在候选者，比如miR-200c，以及治疗靶点的出现，像Tfam,与线粒体呼吸有关，或miR-632，刺激内皮到间质转化。虽然这些发现很有希望，在大型患者队列中进行严格和广泛的验证对于确认其临床相关性和治疗潜力是必不可少的.
