Cardiomyocyte-derived circulating extracellular vesicles allow a non-invasive liquid biopsy of myocardium in health and disease
Spanos, M.; Gokulnath, P.; Li, G.; Hutchins, E.; Meechoovet, B.; Sheng, Q.; Chatterjee, E.; Sharma, R.; Carnel-Amar, N.; Lin, C.; Azzam, C.; Ghaeli, I.; Amancherla, K. V.; Victorino, J. F.; Garcia-Mansfield, K.; Pfeffer, R.; Sahu, P.; Lindman, B. R.; Elmariah, S.; Gamazon, E. R.; Betti, M. J.; Bledsoe, X.; Lance, M. L.; Absi, T.; Su, Y. R.; Do, N.; Contreras, M. G.; Varrias, D.; Kladas, M.; Radulovic, M.; Tsiachris, D.; Spanos, A.; Tsioufis, K.; Ellinor, P. T.; Tucker, N. R.; Januzzi, J. L.; Pirrotte, P.; Jovanovic-Talisman, T.; Keuren-Jensen, K. V.; Shah, R.; Das, S.
Show abstract
The ability to track disease without tissue biopsy in patients is a major goal in biology and medicine. Here, we identify and characterize cardiomyocyte-derived extracellular vesicles in circulation (EVs; "cardiovesicles") through comprehensive studies of induced pluripotent stem cell-derived cardiomyocytes, genetic mouse models, and state-of-the-art mass spectrometry and low-input transcriptomics. These studies identified two markers (POPDC2, CHRNE) enriched on cardiovesicles for biotinylated antibody-based immunocapture. Captured cardiovesicles were enriched in canonical cardiomyocyte transcripts/pathways with distinct profiles based on human disease type (heart failure, myocardial infarction). In paired myocardial tissue-plasma from patients, highly expressed genes in cardiovesicles were largely cardiac-enriched (vs. "bulk" EVs, which were more organ non-specific) with high expression in myocardial tissue by single nuclear RNA-seq, largely in cardiomyocytes. These results demonstrate the first "liquid" biopsy discovery platform to interrogate cardiomyocyte states non-invasively in model systems and in human disease, allowing non-invasive characterization of cardiomyocyte biology for discovery and therapeutic applications.
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