Exosomal miRNA-223-3p as potential biomarkers in patients with cerebral small vessel disease cognitive impairment

Abstract

Background: Cerebrovascular disease is a common clinical illness. Many patients with cerebrovascular disease can be accompanied by cognitive impairment. The exosomal microRNA (miRNA)-223-3p is related to vascular endothelial injury, synaptic function, inflammatory response, and other mechanisms. In this study, we investigated the levels of plasma exosomal miRNA-223-3p in patients with cerebral small vessel disease (CSVD), in order to determine whether it could be used as a more accessible potential biomarker for the early diagnosis and treatment of CSVD. This study aimed to explore whether the development of cognitive impairment can be explained by differentially expressed miRNA-223-3p by detecting the level of miRNA-223-3p, which is abundant in peripheral blood exosomes related to cognitive impairment in CSVD. Methods:The three groups of participants included 40 patients with CSVD cognitive impairment (CSVDCI), 38 patients with CSVD, and 35 normal controls (NC). The real-time polymerase chain reaction (RT-PCR) was used to detect the expression level of blood exosomal miRNA-223-3p. In addition, we also studied the relationship between exosomal miRNA-223-3p and blood Hcy and C-reactive protein (CRP).Receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficacy of plasma exosomal miRNA-223-3p. Results:The expression of exosomal miRNA-223-3p in CSVD increased, and the expression of miRNA-223-3p increased significantly with the occurrence of cognitive impairment. Exosomal miRNA-223-3p was positively correlated with the expression levels of Hcy and CRP in the blood. Conclusions:The expression of plasma exosomal miRNA-223-3p is associated with the development of cognitive impairment in patients with CSVD. It may be involved in the pathogenesis of CSVD and cognitive impairment, and can be used as a sensitive predictive biomarker.

Exosomes for the diagnosis and treatment of dementia

“…There is an increasing interest in exosomes as potential diagnostic agents for exosomes reflect the disease state [28][29][30][31][32][33][34][35][48][49][50][51][52]62,64,65,68,69]. In addition, recent studies give attention to MSC-derived exosomes as potential therapeutic agents due to their immunomodulatory [3 & ] and neuroprotective [70] effects.…”

“…Incubation of microglia with plasma exosomes from PD patients caused activation of microglia through TLR2 and transmission of a-synuclein which is a key protein that contributes to PD pathology [45]. Mutation of a-synuclein resulted in detergent-resistant --Huntingtons disease (HD) --Exosomal mHTT as HD biomarker [62] Exosomes as HD therapeutics [63] Vascular dementia (VaD) --Exosomal miRNA as potential biomarker of VaD [64,65].…”

“…Exosomal miRNA-223-3p expression was increased in plasma of cerebral small vessel disease (CSVD) patients, especially upon the onset of cognitive impairment [64]. Therefore, exosomal miRNA-223-3p can be a potential biomarker of CSVD.…”

Exosomal miR-320e as a Novel Potential Biomarker for Cerebral Small Vessel Disease

“…In the few studies published so far, exosomal miRNA-17 family and miR-223-3p were proved to be closely related to the initiation and development of CSVD. 17 , 18 In the research, we explored exosomal miRNA expression profiles in CSVD patients by high-throughput screening. As miR-668 has been reported to participate in the homeostasis of the NO system, endothelial homeostasis and regulation of inflammatory after ischemia and tissue hypoxia, it suggests that miR-668 may be involved in cerebral small vessel function regulation.…”

“…Studies from Josie C. van Kralingen and Zhao W suggested exosomal miRNA-17 family members and miR-223 are associated with CSVD and CSVD-related cognitive impairment, respectively. 17 , 18 However, there is still a limited amount of studies available, and more investigations are needed to understand the roles of exosomal miRNAs in diagnosis and treatment of CSVD.…”