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Ultrastructural evidence for the formation of amyloid fibrils within cardiomyocytes in isolated atrial amyloid.

Isolated atrial amyloid (IAA) frequently affects elderly human hearts in which only the atria are involved by the deposits. Biochemical analysis has indicated that the major subunit protein of IAA is alpha-human atrial natriuretic peptide (alpha-ANP), which is synthesized by the atrial muscle cells. To define the exact location of the formation of IAA fibrils, right atria from 25 patients undergoing cardiac surgery have been examined by an immunohistochemistry and immunoelectron microscopy with anti-alpha-ANP, apolipoprotein E, amyloid P component, transthyretin, and cathepsin B antisera. Of 25 patients, 19 were involved with IAA deposits which reacted with anti-alpha-ANP, apolipoprotein E, amyloid P component antisera but not with anti-transthyretin antiserum. In 8 of them, amyloid fibrils were seen not only in the interstitium of the atrial myocardium but also in the dilated transverse tubules of the cardiomyocytes. In some cardiomyocytes, amyloid fibrils were also demonstrated within the organelles such as coated and uncoated secretory vesicles or lysosomes. These findings lead to the inescapable conclusion that the polymerization of amyloid fibrils in IAA occurs within the cytoplasm of cardiomyocytes under some conditions.