Exosomal miRNA as an early diagnostic biomarker and potential therapeutic target for cerebral small vessel disease

Abstract

BACKGROUND: In recent years, microRNA (miRNA) has received extensive attention in the pathogenesis and diagnosis and treatment of cerebral small vessel disease, and is involved in the regulation of various pathological processes of cerebral small vessel disease. OBJECTIVE: To review the role of miRNA in the pathogenesis, diagnosis, and treatment of cerebral small vessel disease, and to provide effective therapeutic targets and new potential biomarkers for the early diagnosis of cerebral small vessel disease. METHODS: “microRNA, cerebral small vessel disease, blood-brain barrier, chronic cerebral hypoperfusion, inflammation, apoptosis, diagnosis, biomarkers” were used as English search terms for PubMed search. “Exosomal miRNA, cerebral small vessel disease” were used as Chinese search terms for CNKI search. The search time limit was from inception to January 2025. Through the preliminary screening of reading titles and abstracts, the literature with poor relevance and duplicate content was excluded, and finally 72 articles were included for inductive discussion. RESULTS AND CONCLUSION: (1) Through the excavation and discussion of the biological functions and characteristics of exosomal miRNAs, it was confirmed that exosomal miRNAs are important related components in the occurrence and progression of cerebral small vessel disease diseases. (2) Exosomal miRNA participates in the regulation of various pathological processes of cerebral small vessel disease, playing an important role in the pathological mechanism of cerebral small vessel disease by protecting the blood-brain barrier, improving chronic cerebral hypoperfusion, reducing inflammatory responses, and inhibiting apoptosis. (3) Exosomal miRNA can intervene at different stages of pathological development by targeting multiple signaling pathways, effectively targeting different pathological links of cerebral small vessel disease. (4) The combined use of multiple exosomal miRNAs can effectively improve the progression of cerebral small vessel disease. Different miRNAs play different roles at various stages of the pathological mechanism, and constructing a miRNA interaction network is of great significance for regulating the development of cerebral small vessel disease. (5) Exosomal miRNAs are widely and stably present in various body fluids, and their specific and significant expression in urine, serum, blood and other body fluids of patients with cerebral small vessel disease can serve as an effective basis for diagnosis. (6) Currently, the main clinical treatment is to inject miRNA mimics or antagonists to regulate downstream target gene expression. How to achieve the most effective therapeutic effect of miRNA still requires further research. (7) miRNA as exosomal content has great application prospects in the treatment of cerebral small vessel disease. Future research should further explore its mechanism of action to provide effective ideas and further optimize clinical treatment plans for cerebral small vessel disease.

1. Introduction

Cerebral small vessel disease (CSVD) refers to a series of clinical, imaging, and pathological syndromes caused by various etiologies affecting the cerebral microvasculature or microcirculation, involving small penetrating arteries, arterioles, capillaries, and venules [1]. Epidemiological studies show that CSVD accounts for approximately 20% of strokes and 50%-70% of dementia cases globally, representing 83.8% of all cerebrovascular diseases, and is a major cause of vascular cognitive impairment [2-3]. In recent years, the incidence of CSVD has increased exponentially, with manifestations ranging from asymptomatic covert CSVD to disability and dementia, affecting the quality of life of middle-aged and elderly people worldwide, and is a leading cause of cognitive decline, disability, and death in the elderly [4-7].

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the transcriptional level, influencing cell growth, organ function, and phenotypic symptoms, and alterations in miRNA concentrations can affect cellular activity [8-9]. Studies have confirmed that exosomal miRNAs are novel biomarkers for the diagnosis and treatment of various diseases, involved in multiple neurological disorders and influencing the occurrence of cognitive dysfunction in cerebrovascular diseases [10]. Furthermore, exosomal miRNAs can participate in the pathophysiological processes of cerebrovascular diseases by regulating various signaling pathways, serving as important biomarkers for the prevention and diagnosis of multiple cerebrovascular diseases [11].

This article reviews the role of exosomal miRNAs in the pathogenesis, diagnosis, and treatment of CSVD, aiming to provide effective therapeutic targets and novel potential biomarkers for early diagnosis and prevention, and to offer insights and theoretical basis for optimizing clinical medication and treatment strategies.