© 1999 American Heart Association, Inc.
Integrative Physiology |
Remodeling of Cell-Cell and Cell–Extracellular Matrix Interactions at the Border Zone of Rat Myocardial Infarcts
From the Department of Pathology and Cell Regulation (T.M., M.O., S.M., T.T.) and Second Department of Surgery (T.M., S.M., Y.W., T.O.), Kyoto Prefectural University of Medicine; Department of Anatomy (K.F.), Faculty of Medicine, Kyoto University; and Louis Pasteur Center for Medical Research (Y.Y.), Kyoto, Japan.
Correspondence to Tetsuro Takamatsu, Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto, 602-0841 Japan. E-mail ttakam{at}basic.kpu-m.ac.jp
Abstract—At the border zone of myocardial infarcts, surviving cardiomyocytes achieve drastic remodeling of cell-cell and cell–extracellular matrix interactions. Spatiotemporal changes in these interactions are likely related to each other and possibly have significant impact on cardiac function. To elucidate the changes, we conducted experimental infarction in rats and performed 3-dimensional analysis of the localization of gap junctions (connexin43), desmosomes (desmoplakin), adherens junctions (cadherin), and integrins (ß1-integrin) by immunoconfocal microscopy. After myocardial infarction, changes in the distribution of gap junctions, desmosomes, and adherens junctions showed a similar but nonidentical tendency. In the early phase, gap junctions almost disappeared at stumps (longitudinal edges of cardiomyocytes facing the infarct), and, although desmosomes and adherens junctions decreased, they still remained. In the healing phase, at stumps, connexin43, desmoplakin, and cadherin were closely associated between multiple cell processes originating from a single cardiomyocyte. Electron microscopy confirmed the presence of junctional complexes between the cell processes. ß1-Integrin at the cell process increased during the formation of papillary myotendinous junction–like structures. Abnormal localization of connexin43 was often accompanied by desmoplakin and cadherin on lateral surfaces of surviving cardiomyocytes. These findings suggested that remodeling of gap junction distribution was closely linked to changes in desmosomes and adherens junctions and that temporary formation of intracellular junctional complexes was an element of the remodeling of cell-cell and cell–extracellular matrix interactions after myocardial infarction. Moreover, the remodeling of the intercalated disk region at the myocardial interface with area of scar tissues was associated with the acquisition of extracellular matrix and ß1-integrin.
Key Words: cell junction • intercalated disk • myocardial infarction • remodeling • extracellular matrix
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