BackgroundThe pathological features of aortic dissection (AD) include vascular smooth muscle cell (VSMC) loss, elastic fiber fraction, and inflammatory responses in the aorta. However, little is known about the post-translational modification mechanisms responsible for these biological processes.MethodsA total of 72 aorta samples, used for protein detection, were collected from 36 coronary artery disease (CAD, served as the control) patients and 36 type A AD (TAAD) patients. Chromatin immunoprecipitation (ChIP)-PCR was used to identify the genes regulated by H3K23ac, and tubastatin A, an inhibitor of HDAC6, was utilized to clarify the downstream mechanisms regulated by HDAC6.ResultsWe found that the protein level of histone deacetylase HDAC6 was reduced in the aortas of patients suffering from TAAD and that the protein levels of H4K12ac, and H3K23ac significantly increased, while H3K18ac, H4K8ac, and H4K5ac dramatically decreased when compared with CAD patients. Although H3K23ac, H3K18ac, and H4K8ac increased in the human VSMCs after treatment with the HDAC6 inhibitor tubastatin A, only H3K23ac showed the same results in human tissues. Notably, the results of ChIP-PCR demonstrated that H3K23ac was enriched in extracellular matrix (ECM)-related genes, including Col1A2, Col3A1, CTGF, POSTN, MMP2, TIMP2, and ACTA2, in the aortic samples of TAAD patients. In addition, our results showed that HDAC6 regulates H4K20me2 and p-MEK1/2 in the pathological process of TAAD.ConclusionsThese results indicate that HDAC6 is involved in human TAAD formation by regulating H3K23ac, H4K20me2 and p-MEK1/2, thus, providing a strategy for the treatment of TAAD by targeting protein post-translational modifications (PTMs), chiefly histone PTMs.

中文翻译：

---

HDAC6 与人类主动脉夹层的形成有关

背景主动脉夹层（AD）的病理特征包括血管平滑肌细胞（VSMC）损失、弹性纤维分数和主动脉炎症反应。然而，对负责这些生物过程的翻译后修饰机制知之甚少。 方法从 36 名冠状动脉疾病（CAD，作为对照）患者和 36 名 A 型患者收集了 72 份用于蛋白质检测的主动脉样本。 AD (TAAD) 患者。染色质免疫沉淀 (ChIP)-PCR 用于鉴定 H3K23ac 调控的基因，利用 HDAC6 抑制剂 tubastatin A 阐明 HDAC6 调控的下游机制。 TAAD 患者的主动脉和 H4K12ac 的蛋白质水平，与 CAD 患者相比，H3K23ac 和 H3K23ac 显着增加，而 H3K18ac、H4K8ac 和 H4K5ac 显着减少。尽管 H3K23ac、H3K18ac 和 H4K8ac 在用 HDAC6 抑制剂 tubastatin A 治疗后人 VSMC 中增加，但只有 H3K23ac 在人组织中显示出相同的结果。值得注意的是，ChIP-PCR 的结果表明，在 TAAD 患者的主动脉样本中，H3K23ac 富含细胞外基质 (ECM) 相关基因，包括 Col1A2、Col3A1、CTGF、POSTN、MMP2、TIMP2 和 ACTA2。此外，我们的结果表明，HDAC6 在 TAAD 的病理过程中调节 H4K20me2 和 p-MEK1/2。结论这些结果表明 HDAC6 通过调节 H3K23ac、H4K20me2 和 p-MEK1/2 参与人 TAAD 的形成，因此，