Characterization of Cardiomyocyte-Like Cells in Thoracic Blood Vessels

Abstract

Cardiomyocyte-like cells have been found in pulmonary veins (PV) of mammals, including humans. These cells are implicated as a possible origin of atrial fibrillation, yet their biological nature and physiological function remain poorly understood. We sought 1) to characterize the differentiation states of the cardiomyocyte-like cells in mouse PV during postnatal development, 2) to determine the distribution of cardiomyocyte-like cells in the vasculature, and 3) to investigate contractility of the venous cardiomyocyte-like cells in comparison with that of myocardium. Western blots using monoclonal antibodies recognizing cardiac muscle-specific proteins show that normal cardiac myofilament proteins are expressed at significant levels in PV and azygos vein. The expression of developmentally regulated isoforms of myosin and troponin is synchronized with that in heart. Transgenic mouse lines expressing β-galactosidase under the control of cardiac troponin T promoter show that the cardiomyocyte-like cells in PV reside singly and in clusters discontinuous from the atrial myocardium. Transmission electron microscopy found that the cardiomyocyte-like cells in PV have sarcomeric structures similar to that of ventricular cardiomyocytes. Isolated rat PV contracts upon electrical pacing and responds inotropically to isoproterenol, similarly to that of left atrium strips and ventricular papillary muscle. The paced contractile pattern of rat PV is distinct from the physiological contractions of vascular smooth muscle. Our data demonstrate that the cardiomyocyte-like cells in adult thoracic veins are at a highly differentiated state similar to that of cardiac myocytes in adult hearts. While the role of their excitability in the pathogenesis of atrial fibrillation remains controversial, the ectopic presence of differentiated cardiomyocyte-like cells provides a valuable model to understand the development and differentiation of cardiomyocytes.