Weiss Dar, Means Colin, Mays Gavin, Yeung Nicola, Cavinato Cristina, Manning Edward P, Lam TuKiet T, Humphrey Jay D
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Department of Mechanical Engineering and Materials, University of Denver, Denver, CO, USA.
bioRxiv. 2025 Jun 24:2025.06.18.660413. doi: 10.1101/2025.06.18.660413.
There is a pressing need to identify pathologic mechanisms that render a thoracic aortic aneurysm susceptible to continued enlargement, dissection, or rupture, but additional insight can be gleaned by understanding potential compensatory mechanisms that prevent disease progression and thereby stabilize a lesion. Our biomechanical data suggest that the ascending aorta within a common mouse model of Marfan syndrome, , exhibits progressive disease from 12 weeks to 1 year of age, but near growth arrest from 1 to 2 years of age. Comparison of the biomechanical phenotype, histological characteristics, proteomic signature, and transcriptional profile from 12 weeks to 1 year to 2 years suggests that numerous differentially expressed genes (including downregulated , , and ) and associated proteins may contribute to late-term growth arrest. There is also a conspicuous absence of proteins associated with inflammation from 1 to 2 years of age. Although there is a need to understand better the interconnected roles of temporal changes in differential gene expression and protein abundance, reducing mTOR signaling and reducing excessive inflammation appears to merit increased attention in preventing continued aneurysmal expansion in Marfan syndrome.
迫切需要确定导致胸主动脉瘤易于持续扩大、夹层形成或破裂的病理机制，但通过了解防止疾病进展从而稳定病变的潜在代偿机制，可以获得更多见解。我们的生物力学数据表明，在马凡综合征的常见小鼠模型中，升主动脉在12周龄至1岁时呈现进行性疾病，但在1至2岁时接近生长停滞。对12周龄至1岁至2岁的生物力学表型、组织学特征、蛋白质组学特征和转录谱进行比较，表明许多差异表达基因（包括下调的 、 和 ）及相关蛋白质可能导致后期生长停滞。在1至2岁时也明显缺乏与炎症相关的蛋白质。尽管需要更好地理解差异基因表达和蛋白质丰度的时间变化之间的相互联系，但减少mTOR信号传导和减轻过度炎症似乎在预防马凡综合征中动脉瘤的持续扩张方面值得更多关注。
