Exosomal Composition, Biogenesis and Profiling Using Point-of-Care Diagnostics—Implications for Cardiovascular Disease

Arteriosclerosis is an important age-dependent disease that encompasses atherosclerosis, in-stent restenosis (ISR), pulmonary hypertension, autologous bypass grafting and transplant arteriosclerosis. Endothelial dysfunction and the proliferation of vascular smooth muscle cell (vSMC)-like cells is a critical event in the pathology of arteriosclerotic disease leading to intimal-medial thickening (IMT), lipid retention and vessel remodelling. An important aspect in guiding clinical decision-making is the detection of biomarkers of subclinical arteriosclerosis and early cardiovascular risk. Crucially, relevant biomarkers need to be good indicators of injury which change in their circulating concentrations or structure, signalling functional disturbances. Extracellular vesicles (EVs) are nanosized membraneous vesicles secreted by cells that contain numerous bioactive molecules and act as a means of intercellular communication between different cell populations to maintain tissue homeostasis, gene regulation in recipient cells and the adaptive response to stress. Researchers at Dublin City University focus on the emerging field of EV research in cardiovascular disease (CVD) and discuss how key EV signatures in liquid biopsies may act as early pathological indicators of adaptive lesion formation and arteriosclerotic disease progression. EV profiling has the potential to provide important clinical information to complement current cardiovascular diagnostic platforms that indicate or predict myocardial injury. Finally, the development of fitting devices to enable rapid and/or high-throughput exosomal analysis that require adapted processing procedures will be evaluated.

Diagram of key steps/approaches for measuring exosome for the prediction of CVD

(A) Magnetic microbeads coated with specific antibodies enabled exosome isolation and addition of guanidine-based lysis buffer released the contents of enriched exosomes. Torque-actuated valves and permanent magnets were used to control the process. RNA is adsorbed on a glass-bead filter via electrostatic interactions and reagents are loaded to prepare for qPCR. (B) Images from scanning electron microscope of exosomes captured on antibody-coated magnetic microbeads. Scale bars 500 and 100 nm (inset) (C) Photograph of PDMS iMER cartridge. RT—Reverse transcription.

Burtenshaw D, Regan B, Owen K, Collins D, McEneaney D, Megson IL, Redmond EM, Cahill PA. (2022) Exosomal Composition, Biogenesis and Profiling Using Point-of-Care Diagnostics—Implications for Cardiovascular Disease. Front Cell Dev Biol [Epub ahead of print]. [article]

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