Can MiR-503 be used as a marker in diabetic patients with ischemic stroke?

Abstract

Background Some microRNAs are involved in diabetes pathology and some are known to have role in stroke. MiR-503 causes endothelial dysfunction in diabetic patients, predisposing to ischemia. There has been no study evaluating Mir-503 level in diabetic patients with or without ischemic stroke. Methods We designed a cross-sectional study to assess and compare serum level of MiR-503 in 4 groups of diabetic patients with ischemic stroke (I), non-diabetic patients with stroke (II), diabetic patients (III), and healthy controls (IV) in acute phase and 3 months later. Results Our data analysis showed that mean relative expression of MiR-503 in group (I) was significantly higher than 3 other groups ( p < 0.05). The level of miR-503 was related to the patients’ fasting blood glucose, Cholesterol level, NIHSS score and acute–phase modified Rankin Scale (mRS) (r = 0.49, p = 0.001, r = 0.5, p = 0.009, r = 0.45, p = 0.009, r = 0.48, p = 0.003, CI = 95%). Relative expression of miR in patients with mRS ≤ 2 (good outcome) was lower than in patients with mRS > 2 (poor outcome) ( p = 0.008). After 3 months, level of miR decreased significantly only in group (I) ( p = 0.002). Mean relative expression of miR-503 in chronic phase was not significantly different among groups ( p -value> 0.05). There was no relation between miRNA level and mRS in chronic phase. Conclusion Hyperglycemia and ischemia together raise the level of MiR-503 acutely but it does not remain at high level after 3 months. Although higher miR was related to more disability in acute phase, it does not affect long-term outcome in ischemic patients. As MiR-503 is stable enough in blood it can be used as a potential diagnostic marker of an ischemic stroke in diabetic patient. Its level also is an indicator of stroke severity and patients’ short-term outcome. It is recommended to study whether antagomiR-503 is a new therapeutic agent reducing the severity of and disability due to stroke.

<p>LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway</p>

“… 9 Sheikhbahaei et al reported that miR-503 was stable enough in the blood to be a potential diagnostic marker for ischemic stroke in diabetic patients. 10 The miR-503 in the placenta tissues of patients with gestational diabetes mellitus was significantly up-regulated, and the miR-503 in peripheral blood samples increased, and it was positively correlated with the blood glucose concentration. 11 Yan et al reported that the expression levels of miR-503-5p were significantly associated with diabetes and arterial stenosis.…”

The Causes and Consequences of miR-503 Dysregulation and Its Impact on Cardiovascular Disease and Cancer

“…In EPCs ( Wen et al, 2018 ), miR-503 suppressed angiogenesis by targeting Apelin. In Diabetes mellitus, miR-503 expression level was significantly higher in ischemic muscles and plasma from patients with limb ischemia than normal control ( Caporali et al, 2011 ), and it is also higher in the plasma of diabetic patients with ischemic stroke than that in non-diabetic patients with stroke or in control individuals ( Sheikhbahaei et al, 2019 ). Overexpression of miR-503 suppressed endothelial cells proliferation, migration and network formation by suppression of its targets, cdc25A (cell division cycle 25 A) and CCNE1 (cyclin E1) under normal culture condition ( Caporali et al, 2011 ).…”

Notoginsenoside R1 alleviates high glucose-evoked damage in RSC96 cells through down-regulation of miR-503

“…MiR-503 is a hyperglycaemia-sensitive miRNA that can be highly expressed in diabetic patients [17]. Besides that, miR-503 was considered as a factor in regulating neuro-damage [18], which suggested it acted as a potential therapeutic target in DPN.…”