Liquid biopsy based on blood circulating exosomes provides a promising platform for accurately diagnosing and predicting cardiovascular disease (CVD). To help address the research limitations of exosomes in CVD diagnosis, Creative Biolabs has leveraged its resources to create a "one-stop" service system for exosome research, including extraction and identification, tracing, functional molecular validation, and histological analysis. Our research services related to the application of exosomes in CVD diagnosis provide a new vision for the application of exosomes in CVD diagnosis.

Exosomes as CVD Diagnostic Biomarkers

CVD, as a non-communicable disease, remains one of the leading causes of high mortality worldwide, and the exploration of effective diagnostic strategies is crucial for the timely detection and treatment of CVD. Traditional biomarkers for CVD, such as total cholesterol levels and low-density lipoprotein, can only roughly assess the risk of disease onset and progression, but cannot accurately predict the stage of the pathological process. With the demand for new methods of disease diagnosis such as liquid biopsy in precision medicine, exosomes, mediating intercellular communication in multiple physiopathological states, can be easily isolated from body fluids such as blood and urine as a new source of CVD diagnostic markers. There is strong evidence that exosomes, as bilayer lipid vesicles secreted by most cells, carry bioactive factors and signaling molecules related to multiple CVD pathophysiology with involvement in cardiovascular system development and injury by regulating the expression of related genes. Investigation of epicardial adipose tissue-derived exosomes (eFat-EXO) revealed their high secretion under ventricular fibrillation-promoting (AF) conditions and their pro-inflammatory, pro-fibrotic, and pro-arrhythmic components. Furthermore, the role of circulating exosomes and their cargoes has been suggested to be promising in the diagnostic and prognostic strategies of several CVD pathological processes.

Fig.1 eFat-EVs trigger atrial inflammation, fibrosis, and fibrillation. (Shaihov-Teper, 2021)

Application of Exosomes in CVD Diagnosis Research Service at Creative Biolabs

Exosomes have shown great potential as novel markers for liquid biopsy in the diagnosis of several CVDs, such as coronary artery disease (ACD) and heart failure (HF) disease. Given the biological basis that exosomes and their components are altered in pathological states to reflect the pathological process, the discovery of potential biomarkers for CVD diagnosis is facilitated by the histological analysis and nucleic acid sequencing of exosomes and cargoes. Creative Biolabs applied exosome profiling service for CVD diagnosis aims to inspire new ideas for exosomes as markers in future precision medicine and to improve the research progress of exosomes in CVD diagnosis.

Fig.2 EV diagnostics and various strategies for EV-based therapies. (Sahoo, 2021)

• Discovery of Exosomal miRNAs for CVD Diagnosis

miRNAs are the most common molecules in cardiac, endothelial, and vascular smooth muscle cell-derived exosomes in the cardiovascular system, capable of translocating to receptor cells and altering their function, showing superiority as diagnostic biomarkers for CVD. Exosomes secreted from damaged myocardium and dead cardiomyocytes in ACD found down-regulated expression of miR-939-5p, which is involved in the pathological process of inhibition of angiogenesis by nitric oxide signaling pathway, while up-regulated levels of exosomal miR-133a expression allow for assessment of the extent of myocardial injury and attack cell death. eFat-EXO encapsulated miR-3064-5p was identified closely associated with the regulation of lipogenic differentiation functions in CVD. miR-192, miR-194, and miR34a showed predictive tasks for the development of heart failure and ventricular remodeling. In addition to being used for the prediction of early stages of myocardial infarction, exosomal miRNAs can also serve as candidates for the prognosis of late stages of AVD. For example, the circulating endothelial cell-derived exosome miR-92a-3p has been recognized in the regulation of endothelial and vascular smooth muscle cell phenotypes in ACD. Exosomal overexpression of miR-22, miR-320a, miR-423-5p and miR-92b in HF-associated serum and blood serve as specific biomarkers for the diagnosis and prognosis of systolic heart failure. All of the above demonstrates the potential application of exosomes and their miRNAs for CVD diagnosis.

• Discovery of Exosomal Proteins and Cytokines for CVD diagnosis

In addition to exosome miRNA sequencing-based discovery of potential markers for CVD diagnosis, exosomal proteomic analysis, and cytokine analysis are other complements. There are several exosomal proteins that are upregulated under CVD conditions that have been identified, with significant enrichment of plasma exosome-carrying proteins including C7, C8, C5, complement factor I, complement factor B, and complement factor H components of the complement system, while P-selectin-expressing particles, CD3⁺/CD45⁺, S-MA-α⁺ circulating exosome levels, and exosome-carrying Cystatin C, Serpin F2, and CD14 levels may be important for assessing CVD risk and mortality. In addition, elevated secretion of eFat-EXO and carriage of high levels of pro-inflammatory cytokines such as interleukins and tumor necrosis factor are targets for AF diagnosis.

Research on exosomes in CVD diagnostic applications contributes to the detection and monitoring of pathological progression at an early stage, as well as to effective interventions that can significantly improve cure rates. At Creative Biolabs, our experts keep abreast of the latest developments in exosomes in diagnostic applications and aim to support research on exosomes in CVD diagnostic applications in a multifaceted manner, with our most advanced and comprehensive technology platform. Please contact us to discuss your project.

References

1. Shaihov-Teper, O.; et al. Extracellular vesicles from epicardial fat facilitate atrial fibrillation. Circulation. 2021, 143(25): 2475-2493.
2. Sahoo, S.; et al. Therapeutic and diagnostic translation of extracellular vesicles in cardiovascular diseases: Roadmap to the Clinic. Circulation. 2021, 143(14): 1426-1449.

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