MicroRNA‑29a contributes to intracranial aneurysm by regulating the mitochondrial apoptotic pathway

Zhao,Wenjing; Zhang,Haifang; Su,Jin‑Ying

doi:10.3892/mmr.2018.9257

MicroRNA‑29a contributes to intracranial aneurysm by regulating the mitochondrial apoptotic pathway

Authors:
- Wenjing Zhao
- Haifang Zhang
- Jin‑Ying Su
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Affiliations: First Department of Neurology, Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China, Department of Cardiovascular Medicine, People's Hospital of Handan, Handan, Hebei 056001, P.R. China
Published online on: July 6, 2018 https://doi.org/10.3892/mmr.2018.9257
Pages: 2945-2954

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Abstract

Intracranial aneurysm (IA) is an abnormal expansion in the intracranial arteries that weakens the arterial wall by consistently pushing the vascular wall outwards, which leads to a higher risk of aneurysm rupture. A number of reports have demonstrated that apoptosis is associated with the growth and rupture of IA. MicroRNAs (miRNAs/miRs) perform vital roles in the regulation of the mitochondrial apoptotic pathway and signaling proteins. Increasing evidence has already revealed the role of miR‑29a in injury, including liver injury, cardiovascular injury and ischaemia‑reperfusion injury. However, the role of miR‑29a in IA remains unclear at present. The present study investigated the role of miR‑29a in IA pathogenesis and the underlying mechanisms. By using reverse transcription‑quantitative polymerase chain reaction and western blot analysis, the present study demonstrated that genes, including caspase‑3, ‑8 and ‑9, and proteins, including cytochrome c and myeloid cell leukemia 1 (Mcl‑1), involved in mitochondrial apoptosis pathways were upregulated in IA groups compared with controls. In addition, microarray analysis demonstrated that miR‑29a, one of the most altered miRs in IA mice, was overexpressed in IA mice compared with controls. In vitro experiments revealed that miR‑29a downregulation attenuated human brain vascular smooth muscle cell (HBVSMC) apoptosis, while miR‑29a overexpression increased the apoptosis of HBVSMCs. Furthermore, luciferase reporter analysis revealed that Mcl‑1 is a direct target gene of miR‑29a. An in vivo IA model confirmed that miR‑29a overexpression may promote apoptosis through mitochondrial pathways. It was therefore concluded that miR‑29a may contribute to the progression of IA by regulating mitochondrial apoptotic pathways. Thus, miR‑29a is a potential therapeutic target for IA.

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