In this review, we discuss the application of TEM as a tool for viewing cardiac ultrastructure and how this has been leveraged in cardiovascular studies to visualize complex signaling processes, with a special focus on the mitochondria. In the cardiovascular field, TEM is often used to assist in studies investigating: (1) cardiovascular development and aging (2) cardiovascular disease processes, such as heart failure, myocardial infarction/ischemia (MI), and diabetic cardiomyopathy (3) phenotyping of cardiovascular transgenic models and (4) examination of complex signaling processes, many of which impact mitochondrial function and dynamics, such as apoptosis, autophagy, and mitophagy. TEM has steadily gained popularity in the cardiovascular research field over the last 20 years, being utilized in over 2,000 peer-reviewed cardiovascular research publications ( Figure 1), to examine cardiac ultracellular organization at the nanometer scale. The timeline of the key events in the development and evolution of TEM has been described in an previous study ( Lukasz Mielanczyk et al., 2015). Since the development of the first electron microscope in the 1930's, transmission electron microscopy (TEM) has been an essential technique for the visualization of cellular ultrastructure. The goals of this review are to provide an overview of the current usage of TEM to study cardiac ultrastructural changes to understand how TEM aided the visualization of mitochondria, autophagy, and mitophagy under normal and cardiovascular disease conditions and to discuss the overall advantages and disadvantages of TEM and potential future capabilities and advancements in the field. Recently, the cardiovascular TEM enabled the studying of several signaling processes impacting mitochondrial function, such as mitochondrial fission/fusion, autophagy, mitophagy, lysosomal degradation, and lipophagy. Over the last 20 years, TEM has gained popularity in the cardiovascular field to visualize changes at the nanometer scale in cardiac ultrastructure during cardiovascular development, aging, and a broad range of pathologies. Transmission electron microscopy (TEM) has long been an important technique, capable of high degree resolution and visualization of subcellular structures and organization. 4Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.3Division of Anatomic Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States.2Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States.1Division of Environmental Medicine, Department of Medicine, University of Louisville, KY, United States.Collins 1 †, Mariame Selma Kane 2, Silvio H.
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