TY - JOUR

T1 - Differential Expression of Vascular-Related MicroRNA in Circulating Endothelial Microvesicles in Adults With Spinal Cord Injury

T2 - A Pilot Study

AU - Park, Andrew J

AU - Fandl, Hannah K

AU - Garcia, Vinicius P

AU - Coombs, Geoff B

AU - DeSouza, Noah M

AU - Greiner, Jared J

AU - Barak, Otto F

AU - Mijacika, Tanja

AU - Dujic, Zeljko

AU - Ainslie, Philip N

AU - DeSouza, Christopher A

N1 - ©2023 American Spinal Injury Association.

PY - 2023/4/3

Y1 - 2023/4/3

N2 - BACKGROUND: Spinal cord injury (SCI) is associated with an increased risk and prevalence of cardiopulmonary and cerebrovascular disease-related morbidity and mortality. The factors that initiate, promote, and accelerate vascular diseases and events in SCI are poorly understood. Clinical interest in circulating endothelial cell-derived microvesicles (EMVs) and their microRNA (miRNA) cargo has intensified due to their involvement in endothelial dysfunction, atherosclerosis, and cerebrovascular events.OBJECTIVES: The aim of this study was to determine whether a subset of vascular-related miRNAs is differentially expressed in EMVs isolated from adults with SCI.METHODS: We assessed eight adults with tetraplegia (7 male/1 female; age: 46±4 years; time since injury: 26±5 years) and eight uninjured (6 male/2 female; age: 39±3 years). Circulating EMVs were isolated, enumerated, and collected from plasma by flow cytometry. The expression of vascular-related miRNAs in EMVs was assessed by RT-PCR.RESULTS: Circulating EMV levels were significantly higher (~130%) in adults with SCI compared with uninjured adults. The expression profile of miRNAs in EMVs from adults with SCI were significantly different than uninjured adults and were pathologic in nature. Expression of miR-126, miR-132, and miR-Let-7a were lower (~100-150%; p < .05), whereas miR-30a, miR-145, miR-155, and miR-216 were higher (~125-450%; p < .05) in EMVs from adults with SCI.CONCLUSION: This study is the first examination of EMV miRNA cargo in adults with SCI. The cargo signature of vascular-related miRNAs studied reflects a pathogenic EMV phenotype prone to induce inflammation, atherosclerosis, and vascular dysfunction. EMVs and their miRNA cargo represent a novel biomarker of vascular risk and a potential target for intervention to alleviate vascular-related disease after SCI.

AB - BACKGROUND: Spinal cord injury (SCI) is associated with an increased risk and prevalence of cardiopulmonary and cerebrovascular disease-related morbidity and mortality. The factors that initiate, promote, and accelerate vascular diseases and events in SCI are poorly understood. Clinical interest in circulating endothelial cell-derived microvesicles (EMVs) and their microRNA (miRNA) cargo has intensified due to their involvement in endothelial dysfunction, atherosclerosis, and cerebrovascular events.OBJECTIVES: The aim of this study was to determine whether a subset of vascular-related miRNAs is differentially expressed in EMVs isolated from adults with SCI.METHODS: We assessed eight adults with tetraplegia (7 male/1 female; age: 46±4 years; time since injury: 26±5 years) and eight uninjured (6 male/2 female; age: 39±3 years). Circulating EMVs were isolated, enumerated, and collected from plasma by flow cytometry. The expression of vascular-related miRNAs in EMVs was assessed by RT-PCR.RESULTS: Circulating EMV levels were significantly higher (~130%) in adults with SCI compared with uninjured adults. The expression profile of miRNAs in EMVs from adults with SCI were significantly different than uninjured adults and were pathologic in nature. Expression of miR-126, miR-132, and miR-Let-7a were lower (~100-150%; p < .05), whereas miR-30a, miR-145, miR-155, and miR-216 were higher (~125-450%; p < .05) in EMVs from adults with SCI.CONCLUSION: This study is the first examination of EMV miRNA cargo in adults with SCI. The cargo signature of vascular-related miRNAs studied reflects a pathogenic EMV phenotype prone to induce inflammation, atherosclerosis, and vascular dysfunction. EMVs and their miRNA cargo represent a novel biomarker of vascular risk and a potential target for intervention to alleviate vascular-related disease after SCI.

KW - Humans

KW - Male

KW - Female

KW - MicroRNAs/genetics

KW - Pilot Projects

KW - Spinal Cord Injuries/metabolism

KW - Cell-Derived Microparticles/metabolism

KW - Atherosclerosis/metabolism

U2 - 10.46292/sci22-00032

DO - 10.46292/sci22-00032

M3 - Article

C2 - 37235195

VL - 29

SP - 34

EP - 42

JO - Topics in spinal cord injury rehabilitation

JF - Topics in spinal cord injury rehabilitation

SN - 1082-0744

IS - 2

ER -