Key result
Downregulation of MALAT1 expression in vivo exacerbated cerebral ischemic injury, significantly increasing infarct volumes and neurological deficits (P < 0.05) while suppressing angiogenesis.
Why the study?
MALAT1 had been reported to potentially protect against cerebral ischemic injury, but its role and underlying mechanism in ischemic stroke remained to be investigated.
Does MALAT1 modulation affect angiogenesis and cerebral ischemic injury in mouse and cell models of ischemic stroke?
Does MALAT1 modulation affect angiogenesis and cerebral ischemic injury in mouse and cell models of ischemic stroke?
p-value: p=<0.05
MALAT1 promotes angiogenesis and protects against cerebral ischemic injury via the caveolin-1/VEGF pathway, suggesting it as a potential therapeutic target for ischemic stroke.
Animal findings preclude clinical translation; leaves open MALAT1 as a therapeutic target in human stroke.
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA (lncRNA), has been reported to potentially protect against cerebral ischemic injury. We investigated the role and underlying mechanism of MALAT1 in ischemic stroke. A mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a human brain microvascular endothelial cell (HBMEC) model of oxygen-glucose deprivation/reoxygenation (OGD/R) were established. The Zea Longa 5-point scale, VEGFR2/CD34 double immunofluorescence (IF), TUNEL staining, cell counting kit-8 (CCK-8) assay, tube formation assay, Transwell assay, and qRT–PCR were used to evaluate neurological deficits, endothelial cell (EC) proliferation, cell apoptosis, cell viability, in vitro angiogenesis, cell migration, and MALAT1 levels in mice, respectively. MALAT1 was found to promote cell migration and tube formation in vitro by affecting the caveolin-1/VEGF pathway. Downregulation of MALAT1 expression in vivo exacerbated cerebral ischemic injury as manifested by severe neurological deficits, elevation of apoptosis, and a decrease in the number of VEGFR2 + /CD34 + endothelial progenitor cells (EPCs). These findings indicated that MALAT1 may promote angiogenesis after cerebral ischemic injury via the caveolin-1/VEGF pathway, thereby suggesting that MALAT1 is a therapeutic target for ischemic stroke.
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Lin et al. (2023) studied Ischemic stroke (n=134). MALAT1 knockdown (shMALAT1 lentivirus) vs. Negative control lentivirus was evaluated on Cerebral infarct volume and neurological deficits (p=<0.05). Downregulation of MALAT1 expression in vivo exacerbated cerebral ischemic injury, significantly increasing infarct volumes and neurological deficits (P < 0.05) while suppressing angiogenesis.
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