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微小RNA在动脉粥样硬化性和非动脉粥样硬化性主动脉瘤中对细胞表型和壁重塑的调控:差异与相似性

miRNA Regulation of Cell Phenotype and Parietal Remodeling in Atherosclerotic and Non-Atherosclerotic Aortic Aneurysms: Differences and Similarities.

作者信息

Terriaca Sonia, Ferlosio Amedeo, Scioli Maria Giovanna, Coppa Francesca, Bertoldo Fabio, Pisano Calogera, Belmonte Beatrice, Balistreri Carmela Rita, Orlandi Augusto

机构信息

Anatomic Pathology, Policlinico Tor Vergata, 00133 Rome, Italy.

Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University, 00133 Rome, Italy.

出版信息

Int J Mol Sci. 2024 Feb 24;25(5):2641. doi: 10.3390/ijms25052641.

Abstract

Aortic aneurysms are a serious health concern as their rupture leads to high morbidity and mortality. Abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms (TAAs) exhibit differences and similarities in their pathophysiological and pathogenetic features. AAA is a multifactorial disease, mainly associated with atherosclerosis, characterized by a relevant inflammatory response and calcification. TAA is rarely associated with atherosclerosis and in some cases is associated with genetic mutations such as Marfan syndrome (MFS) and bicuspid aortic valve (BAV). MFS-related and non-genetic or sporadic TAA share aortic degeneration with endothelial-to-mesenchymal transition (End-Mt) and fibrosis, whereas in BAV TAA, aortic degeneration with calcification prevails. microRNA (miRNAs) contribute to the regulation of aneurysmatic aortic remodeling. miRNAs are a class of non-coding RNAs, which post-transcriptionally regulate gene expression. In this review, we report the involvement of deregulated miRNAs in the different aortic remodeling characterizing AAAs and TAAs. In AAA, miRNA deregulation appears to be involved in parietal inflammatory response, smooth muscle cell (SMC) apoptosis and aortic wall calcification. In sporadic and MFS-related TAA, miRNA deregulation promotes End-Mt, SMC myofibroblastic phenotypic switching and fibrosis with glycosaminoglycan accumulation. In BAV TAA, miRNA deregulation sustains aortic calcification. Those differences may support the development of more personalized therapeutic approaches.

摘要

主动脉瘤是一个严重的健康问题,因为其破裂会导致高发病率和死亡率。腹主动脉瘤(AAA)和胸主动脉瘤(TAA)在病理生理和发病机制特征上既有差异又有相似之处。AAA是一种多因素疾病,主要与动脉粥样硬化相关,其特征为相关的炎症反应和钙化。TAA很少与动脉粥样硬化相关,在某些情况下与基因突变有关,如马凡综合征(MFS)和二叶式主动脉瓣(BAV)。与MFS相关的以及非遗传或散发性TAA与具有内皮-间充质转化(End-Mt)和纤维化的主动脉退变相关,而在BAV TAA中,以伴有钙化的主动脉退变为主。微小RNA(miRNA)有助于调节动脉瘤性主动脉重塑。miRNA是一类非编码RNA,可在转录后调节基因表达。在本综述中,我们报告了失调的miRNA参与AAA和TAA不同的主动脉重塑过程。在AAA中,miRNA失调似乎参与了壁层炎症反应、平滑肌细胞(SMC)凋亡和主动脉壁钙化。在散发性和与MFS相关的TAA中,miRNA失调促进End-Mt、SMC肌成纤维细胞表型转换以及伴有糖胺聚糖积聚的纤维化。在BAV TAA中,miRNA失调维持主动脉钙化。这些差异可能有助于开发更具个性化 的治疗方法。

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