Cardiomyocyte-derived circulating extracellular vesicles allow a non-invasive liquid biopsy of myocardium in health and disease

作者：Michail Spanos, Priyanka Gokulnath, Guoping Li, Elizabeth Hutchins, Bessie Meechoovet, Quanhu Sheng, Emeli Chatterjee, Ritin Sharma, Natacha Carnel-Amar, Claire Lin, Christopher Azzam, Ima Ghaeli, Kaushik Amancherla, José Fabian Victorino, Krystine Garcia‐Mansfield, Ryan Pfeffer, Parul Sahu, Brian R. Lindman, Sammy Elmariah, Eric R. Gamazon, Michael J. Betti, Xavier Bledsoe, Michelle L Lance, Tarek Absi, Yan Su, Ngoc Do, Marta García-Contreras, Dimitrios Varrias, Michail Kladas, Miroslav Radulovic, Dimitris Tsiachris, A. Spanos, Konstantinos Tsioufis, Patrick T. Ellinor, Nathan R. Tucker, James L. Januzzi, Patrick Pirrotte, Tijana Jovanović‐Talisman, Kendall Van Keuren‐Jensen, Ravi V. Shah, Saumya Das · 发表于：medRxiv · 年份：2024 · DOI：10.1101/2024.09.19.24314009 · 被引用次数：6 · 研究领域：Extracellular vesicles in disease、Cardiovascular Effects of Exercise、Advancements in Semiconductor Devices and Circuit Design

SUMMARY 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.