Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers

Abstract

Cardiovascular diseases (CVD) represent the leading cause of morbidity and mortality globally. The emerging role of extracellular vesicles (EVs) in intercellular communication has stimulated renewed interest in exploring the potential application of EVs as tools for diagnosis, prognosis, and therapy in CVD. The ubiquitous nature of EVs in biological fluids presents a technological advantage compared to current diagnostic tools by virtue of their notable stability. EV contents, such as proteins and microRNAs, represent specific signatures of cellular activation or injury. This feature positions EVs as an alternative source of biomarkers. Furthermore, their intrinsic activity and immunomodulatory properties offer EVs unique opportunities to act as therapeutic agents per se or to serve as drug delivery carriers by acting as miniaturized vehicles incorporating bioactive molecules. In this article, we aim to review the recent advances and applications of EV-based biomarkers and therapeutics. In addition, the potential of EVs as a drug delivery and theranostic platform for CVD will also be discussed.

Keywords: biomarker; cardiovascular disease; drug delivery; extracellular vesicles; theranostics; therapeutic.

Figure 1

Schematic diagram illustrating EVs as an alternative source of biomarkers in cardiovascular disease (CVD). Extracellular vesicle (EV) proteins, such as CD14, cystatin C and coagulation-related proteins including Serpin G1 and Serpin F2, have been proposed as novel biomarkers for diagnosis and prognosis of heart failure, vascular disease, and stroke. Conventional CVD risk factors, such as obesity and smoking, have been associated with EV protein contents, including CD14, cystatin C, and procoagulant proteins. Certain EV miRNAs have also been identified as novel diagnostic and prognostic biomarkers for stroke and heart failure. Five EV miRNAs are listed as representatives. EV lipids, however, remain largely unexplored in the diagnosis or prognosis of CVD. CVD, cardiovascular diseases; CS, complement system; C5a, complement factor 5a; pIgR, polygenic immunoglobulin receptor; PS, phosphatidylserine; PE, phosphatidylethanolamine.

Figure 2

Potential applications of EVs in diagnostic, therapeutic, and drug delivery in CVD. Increasing novel biomarkers identified in EVs have made them as attractive alternative sources of biomarkers for a variety of CVD. On the other hand, EVs also bear intrinsic therapeutic activities and great potential to deliver drugs or therapeutic compounds and therefore, may offer synergistic treatment effects. Endogenous EV biomarkers and/or loaded diagnostic agents may be housed together with therapeutic compounds to create theranostic EVs for CVD treatment. STEMI, ST-elevation myocardial infarction.