Electron microscopy analysis of endothelial-to-mesenchymal transition in native and prosthetic blood vessels and heart valves

Aim . To analyse the electron microscopy signs of endothelial-to-mesenchymal transition (EndoMT) in endothelial cells (ECs) of native blood vessels and medical devices for cardiovascular surgery (including vascular patches, stents, and bioprosthetic heart valves) for assessing the role of EndoMT in the pathogenesis of implantation-associated long-term complications. Materials and Methods . To achieve this task, we interrogated internal thoracic artery used as a coronary bypass conduit, ovine carotid artery with a xenopericardial patch, stented human carotid artery, and bioprosthetic aortic valve. The tissues were stained with heavy metals, embedded into epoxy resin, grinded and polished, sputter coated with carbon, and visualised using backscattered scanning electron microscopy (EM-BSEM technique). Results . All samples contained both physiological ECs and the cells undergoing EndoMT. Physiological ECs retained apicobasal polarity, elongated nucleus, and intact basement membrane. Cells undergoing EndoMT had polymorphic nuclei, loss of apicobasal polarity, degraded and disintegrated basement membrane and internal elastic lamina, and migration into the vascular wall. Numerous immune cells (i.e., neutrophils, eosinophils, and macrophages) in the subendothelial layer indicated distinct stages of inflammation and vascular or valvular remodeling. Cell undergoing EndoMT migrated into the medial layer acquiring a myofibroblastic phenotype. Conclusion . These results confirm the role of EndoMT in the pathogenesis of the complications associated with the implantation of medical devices. Signs of dysfunctional ECs and EndoMT have been accompanied by inflammation, extracellular matrix degradation, and disruption of endothelial barrier altogether promoting intimal hyperplasia and restenosis as well as structural valve deterioration. These data require the detailed investigation of EndoMT molecular mechanisms and therapeutic approaches of its prevention in patients undergoing cardiovascular surgery interventions.