Abstract
(1) Background: Circulating micro-RNAs (miRNAs) modulate the expression of molecules in diabetes. We evaluated the expression of serum miRNA-195-5p and -451a in diabetic patients with ischemic stroke and correlated them with two markers of brain tissue integrity. (2) Methods: Seventy-eight subjects with acute ischemic stroke (AIS) or transient ischemic attack (TIA) (40 with diabetes) were enrolled. Serum miRNA levels, brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGF-A) were assessed at admission and 24 and 72 h after a post-ischemic stroke, and were compared to 20 controls. (3) Results: Both circulating miRNAs were two-fold up-regulated in diabetic AIS and TIA patients compared to non-diabetics. Their levels progressively decreased at 24 and 72 h in both AIS and TIA patients. Interestingly, in the non-diabetic TIA group, both circulating miRNAs, although higher than the controls, tended to achieve a complete decay after 72 h. Furthermore, miRNA-195-5p and miRNA-451a levels inversely correlated with both BDNF and VEGF-A serum levels. (4) Conclusions: These data show a different profile of both micro-RNAs in diabetic versus non-diabetic patients after acute ischemic stroke, suggesting their pivotal role in cerebrovascular ischemic attack.
Highlights
Previous data have reported the involvement of several micro-RNAs in post-ischemic angiogenesis as a crucial step to restore blood supply to ischemic cerebral regions after stroke [1,2].Among them, hypoxia-regulated miRNAs (HRMs) play a crucial role, since they are highly expressed following cerebral hypoxic conditions, due to cerebral blood flow reduction [3].In particular, cerebral HRMs, such as miRNA-195-5p and miRNA-451a, have been both reported to suppress vascular endothelial growth factor A (VEGF-A) levels, thereby reducing new vessel formation in hepatocellular carcinoma in a rat brain after stroke [4,5,6]
We previously reported an increased expression of circulating miRNA-195-5p and miRNA-451a levels in patients with both acute ischemic stroke (AIS) and transient ischemic attack (TIA) at admission [6]
In diabetic patients with TIA, an increased expression in miRNA-451a was associated with lower levels of circulating VEGF-A and this was even more markedly reduced in diabetic patients with AIS
Summary
Previous data have reported the involvement of several micro-RNAs (miRNAs) in post-ischemic angiogenesis as a crucial step to restore blood supply to ischemic cerebral regions after stroke [1,2].Among them, hypoxia-regulated miRNAs (HRMs) play a crucial role, since they are highly expressed following cerebral hypoxic conditions, due to cerebral blood flow reduction [3].In particular, cerebral HRMs, such as miRNA-195-5p and miRNA-451a, have been both reported to suppress vascular endothelial growth factor A (VEGF-A) levels, thereby reducing new vessel formation in hepatocellular carcinoma in a rat brain after stroke [4,5,6]. Previous data have reported the involvement of several micro-RNAs (miRNAs) in post-ischemic angiogenesis as a crucial step to restore blood supply to ischemic cerebral regions after stroke [1,2]. We previously reported an increased expression of circulating miRNA-195-5p and miRNA-451a levels in patients with both acute ischemic stroke (AIS) and transient ischemic attack (TIA) at admission [6]. As a matter of fact, angiogenesis is crucial to restore blood flow to the ischemic cerebral area, and to promote neurogenesis and to improve neurological functions [7]. To the best of our knowledge, no data have been reported on the possible changes in circulating miRNA-195-5p and miRNA-451a levels in diabetic patients with AIS
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