Chou Elizabeth L, Lino Cardenas Christian L, Chaffin Mark, Arduini Alessandro D, Juric Dejan, Stone James R, LaMuraglia Glenn M, Eagleton Matthew J, Conrad Mark F, Isselbacher Eric M, Ellinor Patrick T, Lindsay Mark E
Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, Mass.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, Mass.
JVS Vasc Sci. 2021 Dec 7;3:41-47. doi: 10.1016/j.jvssci.2021.11.002. eCollection 2022.
Carotid plaque instability contributes to large vessel ischemic stroke. Although vascular smooth muscle cells (VSMCs) affect atherosclerotic growth and instability, no treatments aimed at improving VSMC function are available. Large genetic studies investigating atherosclerosis and carotid disease in relation to the risk of stroke have implicated polymorphisms at the locus. The HDAC9 protein has been shown to affect the VSMC phenotype; however, how this might affect carotid disease is unknown. We conducted a pilot investigation using single nuclei RNA sequencing of human carotid tissue to identify cells expressing HDAC9 and specifically investigate the role of the HDAC9 in carotid atherosclerosis. We found that carotid VSMCs express HDAC9 and genes typically associated with immune characteristics. Using cellular assays, we have demonstrated that recruitment of macrophages can be modulated by HDAC9 expression. HDAC9 expression might affect carotid plaque stability and progression through its effects on the VSMC phenotype and recruitment of immune cells.
颈动脉斑块不稳定会导致大血管缺血性中风。尽管血管平滑肌细胞（VSMC）会影响动脉粥样硬化的发展和不稳定性，但目前尚无旨在改善VSMC功能的治疗方法。针对动脉粥样硬化和颈动脉疾病与中风风险关系的大型基因研究表明，该基因座存在多态性。已有研究表明HDAC9蛋白会影响VSMC表型；然而，其如何影响颈动脉疾病尚不清楚。我们进行了一项初步研究，利用人颈动脉组织的单核RNA测序来鉴定表达HDAC9的细胞，并具体研究HDAC9在颈动脉粥样硬化中的作用。我们发现颈动脉VSMC表达HDAC9以及通常与免疫特征相关的基因。通过细胞实验，我们证明巨噬细胞的募集可受HDAC9表达的调节。HDAC9表达可能通过影响VSMC表型和免疫细胞募集来影响颈动脉斑块的稳定性和进展。
