Novel “genetic signature” for stroke identified
MedWire News: Italian researchers report a novel "genetic signature" for atherosclerotic plaque that could provide a possible treatment target for stroke.
The team found that expression of five microRNAs (miRNAs) - small endogenous RNAs that regulate gene expression - was associated with an unstable plaque phenotype, leading to plaque rupture and acute clinical events such as stroke.
This "indicate[s] a potential role for miRNAs in the homeostasis of atherosclerotic plaques," remark Francesco Cipollone (G d'Annunzio University, Chieti) and colleagues.
In addition, these findings "identify a new potential pharmacological target for plaque stabilization and raise the interesting possibility… that selective modification in this miRNA signature might provide a novel form of therapy for plaque stabilization in humans," they say.
The researchers performed a large-scale analysis of miRNA expression in 15 plaques collected from patients who underwent carotid endarterectomy in Chieti Hospital, Italy. Of the 41 miRNAs examined, the team found that expression of five miRNAs (miRNA-100, miRNA-127, miRNA-145, miRNA-133a, and miRNA-133b) was significantly greater in symptomatic (n=7) compared with asymptomatic plaques (n=8).
These findings were confirmed in a separate series of 38 plaques collected from patients who underwent carotid endarterectomy at Ancona Hospital in Italy.
To confirm the biological relevance of the identified miRNAs, Cipollone et al performed in vitro analysis on human umbilical vein endothelial cells (HUVECs). The HUVECs were transfected with miRNA-145 and miRNA-133a and the respective levels of their target gene products, plasminogen activator inhibitor-1 (PAI-1) and matrix metallopeptidase 9 (MMP-9), were assessed. Of note, PAI-1 and MMP-9 have previously been shown to play a role in atherosclerosis.
Compared with control (nontransfected) cells, HUVECs transfected with miRNA-145 expressed 38% and 63% less PAI-1 protein after 8 and 24 hours of incubation, respectively. Similarly, levels of MMP-9 were 49% and 38% lower in miRNA-133a-transfected HUVECs than in control cells.
Cipollone and co-investigators suggest their results "confirm the ability of miRNAs in regulating target protein expression." They add that their findings rule out the hypothesis that "miRNA alteration in symptomatic plaques is simply an epiphenomenon without any practical readout."
They hope, now that they have identified a specific miRNA signature for stroke, to identify previously unrecognized molecular targets that could lead to "innovative therapeutic approaches in stroke."
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By Nikki Withers