Cardiovascular diseases (CVDs) continue to dominate global mortality statistics, with immune dysregulation emerging as a central feature in their pathogenesis. This review by Gareev et al. focuses on immune-derived microRNAs (immuno-miRs) as pivotal modulators of immune responses in cardiovascular settings, highlighting their roles in pathophysiology, diagnostic potential, and therapeutic promise.
Introduction
The authors introduce CVDs as a global health crisis, exacerbated by the interplay between immune dysregulation and cardiovascular remodeling. Immune cells like macrophages and T cells, while crucial for homeostasis, can trigger chronic inflammation, fibrosis, and plaque instability when misregulated. Recent discoveries spotlight miRNAs, small non-coding RNAs secreted by immune cells, as key players in controlling these immune responses through gene silencing.
miRNAs in Immune Cell Development and Function
Immuno-miRs regulate both innate and adaptive immune responses, influencing the development, activation, and function of various immune cells.
Intercellular Communication via Extracellular Vesicles
The review explores how immune cells secrete extracellular vesicles (EVs) loaded with miRNAs, enabling communication with cardiomyocytes, endothelial cells, and other immune cells. For example, miR-223-enriched EVs reduce endothelial inflammation, while miR-155-containing EVs amplify pathological responses. This mode of communication underscores miRNAs' potential as therapeutic targets and biomarkers.
miRNAs and Cardiovascular Risk Factors
miRNAs modulate inflammation across major CVD risk factors:
The authors highlight how dysregulated miRNAs interconnect these risk factors, making them potential biomarkers for early detection and targets for prevention.
miRNA Regulation of Specific Immune Cells in CVDs
The review provides detailed mechanistic insights into how miRNAs regulate individual immune cell types in cardiovascular pathology:
miR-181a supports T cell activation; its decline contributes to immune senescence in aging.
miR-155 demonstrates dual roles, being pro-inflammatory in macrophages but essential for Treg proliferation and suppression.
CTLA-4 Signaling and Its miRNA Regulation
The article explores the CTLA-4 immune checkpoint, crucial for tempering T cell activation. CTLA-4 is regulated by miRNAs including miR-155, miR-9, miR-105, and miR-487a-3p. Targeting these regulatory axes may enhance Treg function, reduce vascular inflammation, and improve outcomes post-myocardial infarction.
Clinical Implications and Therapeutic Potential
The authors detail miRNA-based therapies, such as:
Circulating miRNAs, due to their stability and specificity, are emerging as non-invasive biomarkers for diagnosis and prognosis across CVD subtypes, including heart failure and atherosclerosis.
Future Directions and Limitations
Despite compelling preclinical data, several challenges remain:
Future research must refine miRNA delivery platforms, conduct larger clinical trials, and integrate miRNA profiling into personalized cardiovascular care.
Conclusion
Immuno-miRs represent a transformative opportunity in cardiovascular medicine. They serve as crucial regulators of immune responses, promising biomarkers, and emerging therapeutic targets. Harnessing their full potential could revolutionize the early diagnosis, risk assessment, and treatment of CVDs in a minimally invasive and precision-guided manner.
Gene Expression (GE) is an open-access journal. It was launched in 1991 by Chicago Medical School Press, and transferred to Cognizant Communication Corporation in 1994. From August 2022, GE is published by Xia & He Publishing Inc.
GE publishes peer-reviewed and high-quality original articles, reviews, editorials, commentaries, and opinions on its primary research topics including cell biology, molecular biology, genes, and genetics, especially on the cellular and molecular mechanisms of human diseases.
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