Long Noncoding RNA Malat1 Regulates Cerebrovascular Pathologies in Ischemic Stroke

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• MicroRNAs are known to regulate vascular and neural damage in ischemic stroke.
• The role of other noncoding RNAs, such as long noncoding RNAs (lncRNAs), in cerebrovascular pathophysiology remains less understood.
• Metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was initially identified as a prognostic marker in lung cancer.

Purpose of the Study:

• To investigate the role of the lncRNA Malat1 in the outcome of ischemic stroke.
• To elucidate the underlying molecular mechanisms by which Malat1 influences brain injury after stroke.
• To explore the potential of Malat1 as a therapeutic target for ischemic stroke.

Main Methods:

• Primary mouse brain microvascular endothelial cells (BMECs) were treated with Malat1 GapmeR and subjected to oxygen-glucose deprivation (OGD).
• Malat1 knockout (KO) and wild-type (WT) mice underwent middle cerebral artery occlusion (MCAO) followed by reperfusion.
• Cell death, apoptotic factors (Bim), inflammatory cytokines (MCP-1, IL-6, E-selectin), and Malat1-factor interactions were assessed using LDH, MTT, qPCR, ELISA, Western blotting, and RNA immunoprecipitation.

Main Results:

• Malat1 expression increased in BMECs after OGD and in cerebral microvessels after MCAO.
• Malat1 silencing in BMECs exacerbated OGD-induced cell death and increased proapoptotic and inflammatory factors.
• Malat1 KO mice exhibited larger infarct volumes, worsened neurological deficits, and elevated proapoptotic and inflammatory markers compared to WT mice.
• Malat1 was found to bind to Bim and E-selectin both in vitro and in vivo.

Conclusions:

• Malat1 plays a significant protective role in ischemic stroke by exerting anti-apoptotic and anti-inflammatory effects.
• Malat1 reduces ischemic cerebral vascular and parenchymal damage.
• lncRNAs, including Malat1, represent a potential therapeutic avenue for minimizing brain damage after stroke.