Circulating microRNAs, Vascular Risk, and Physical Activity in Spinal Cord-Injured Subjects

Abstract

The aim of this study was to compare the expression of serum microRNAs (miRNAs) in individuals with spinal cord injury (SCI) (athletes [SCI-A] and sedentary [SCI-S]) and able-bodied (AB) individuals, and investigate the relationship of miRNAs with carotid intima-media thickness (cIMT) and serum oxidized LDL-cholesterol (oxLDL) among SCI subjects. Seventeen SCI-S, 23 SCI-A, and 22 AB males were evaluated by clinical and laboratory analysis, and had oxLDL and cIMT measured by enzyme-linked immunosorbent assay (ELISA) and ultrasonography, respectively. A total of 754 miRNAs were measured using a TaqMan OpenArray Human MicroRNA system. SCI-S subjects had higher cIMT and oxLDL than SCI-A and AB. Compared with AB, only one miRNA was differently expressed in both SCI-A and SCI-S individuals, whereas 25 miRNAs were differently expressed in SCI-S, but not in SCI-A. Of these 25 miRNAs, 22 showed different expression between SCI-S and SCI-A. Several miRNAs correlated with oxLDL and cIMT among all SCI individuals. Notably, miR-125b-5p, miR-146a-5p, miR-328-3p, miR-191-5p, miR-103a-3p, and miR-30b-5p correlated with both oxLDL and cIMT, and showed distinct expression between the SCI-A and SCI-S groups. Gene set enrichment analysis demonstrated that miRNAs related to cIMT and oxLDL may be involved in molecular pathways regulating vascular function and remodeling. In conclusion, this exploratory analysis suggests that variations in circulating miRNA expression in individuals with SCI compared with AB subjects are markedly attenuated by regular physical activity. Several miRNAs may be involved in physical activity-related improvements in vascular risk and remodeling among SCI individuals.

Down-regulation of miR-30b-5p protects cardiomyocytes against hypoxia-induced injury by targeting Aven

“…Downregulation of miR-30b-5p alleviated hypoxia-induced cardiomyocyte injury, observed as increased cell viability, decreased LDH leakage, and a decreased apoptosis rate. Consistently, miR-30b-5p is correlated with physical activity-related improvements in vascular risk and remodeling [22]. Surprisingly, Aven was a target gene of miR-30b-5p and Aven knockdown showed a similar effect on cardiomyocytes.…”

Noninvasive imaging assessment of rehabilitation therapy in heart failure with preserved and reduced left ventricular ejection fraction (IMAGING-REHAB-HF): design and rationale

“…At baseline, the expression of serum miRNAs will be assessed using the TaqMan OpenArray Human MicroRNA system, a quantitative polymerase chain reaction (qPCR)-based miRNA array platform that contains 754 microRNAs on a microfluidic platform across two sets of primer pools, panel A and B (Life Technologies, Carlsbad, Californina, USA), as previously reported. 54 The serum expression of miRNAs that show different expression between the HFpEF and HFrEF groups at baseline will be reanalyzed by real-time PCR after the rehabilitation program in HF patients. Recently, a series of circulating miRNA were shown to provide adequate differentiation between HFrEF and HFpEF, 55,56 enhancing the characterization of HF subtypes over traditional biochemical and imaging biomarkers.…”

“…Based on this observation, we will evaluate whether any miRNA evaluated at baseline will predict changes in CPET, MRI and NT-pro-BNP analyses after the rehabilitation program. 54…”

Spinal Cord Injury: A Study Protocol for a Systematic Review and Meta-analysis of microRNA Alterations

“…We and others have also shown that miRNA levels in cerebrospinal uid (CSF) and blood serum are speci cally altered in SCI in a severity-dependent fashion, both in humans [20], and in animal models [13,21]. miRNAs are furthermore differentially altered in chronic SCI patients undergoing active exercise regimes, compared to sedentary patients [22]. miRNAs are promising biomarkers of injury severity, and by implication -recovery and response to treatment [23][24][25] due to their regional abundance, speci c developmental requirements, and altered levels following SCI.…”