Local changes in myosin types in diseased human atrial myocardium: a quantitative immunofluorescence study.

Abstract

Two monoclonal antibody groups were prepared from adult human atrial and ventricular myosin heavy chains. Using these two groups, we were able to identify two myosin variants in human atria and to classify human atrial fibers into a-, mixed, or /S-fibers according to the reactivity of the two monoclonal antibody groups to a-and /-myosin heavy chains of normal young and hypothyroid rat ventricles, respectively. The a-fiber percentage of the left atria in two normal human hearts was 15% higher than in the right atria. The auricles contained two to three times more a-fibers than /3-fibers, whereas the proportion was reversed in the crista terminalis. The mean fiber diameter of the aand /-fibers was 13.6 + 3 gm. A complete a-to /-fiber transition was observed in all atrial regions of two hearts with severe ventricular myocardial infarction; a moderate a-to /3-fiber transition was observed only in the left atria of two hearts with primary congestive cardiomyopathy. The mean diameters of the two fiber types were significantly increased in all diseased hearts (1 9 ± 3.8 ,gm). We hypothesize that pressure overload and increased wall tension successively induce an enlargement of the fiber diameter and an a-to /3-myosin transition. Circulation 72, No. 2, [272][273][274][275][276][277][278][279] 1985.AT LEAST TWO molecular variants of myosin heavy chains have been identified in normal human atrial myocardium by histochemical and indirect immunofluorescence studies involving polyclonal and monoclonal antibodies.>1 We have referred to the human atrial myosin, which reacts strongly with one set of our monoclonal antibodies, as "/3-like" atrial myosin since this set of monoclonal antibodies strongly reacts with ventricular,8-myosin in hypothyroid rats.3 This human atrial :-like myosin variant has been separated from the other myosin form by immunochromatography, and it has been shown that each form of human atrial myosin has a different primary structure but the same high enzymatic activity in vitro.5 No direct evidence concerning any immunologic cross-reactivity of the other human atrial myosin with rat ventricular a-myosin is available at present. The fibers containing either /3-like myosin or the other myosin form are not randomly distributed within the different regions of the atria in normal hearts, and marked changes in their local distributions have been described in diseased human hearts.2 3 Neither the distribution of the two fiber types in the different atrial regions nor their pathologic modifications have ever been quantified.In this study we used, for the first time, two groups of monoclonal antibodies that specifically detect each atrial myosin variant in the rat heart as well as in the human heart. We also quantified the fiber type distributions within different regions of the atria in two normal and four diseased human hearts. In the latter, different isomyosin distributions were shown to be related to different pathologic conditions. Materials and methodsPatients. Four adult human hearts were obtained...

Distribution pattern of α and β myosin in normal and diseased human ventricular myocardium

“…Finally two to four tissue samples were also randomly excised from other areas in each ventricle. Tissue samples were frozen in precooled isopentane or directly in liquid nitrogen, as previously described (1,2).…”

“…Three groups of monoclonal antibodies whose specificity has already been described (1,2,5,6,7,17) were used in this study. According to their reactivity with rat myosin, they were referred to as anti-ct and anti-13 myosin.…”

“…Control experiments and indirect immunofluorescence processing (fluorescein goat antimousc IgG specially prepared from human tissue) (Nordic Immunological Laboratories, Tilburg, The Netherlands) were done as previously described (1,2). Sections were examined with a Leitz microscope equipped with epifluorescence optics.…”

“…In a recent study (2), using monoclonal antibodies specific for each human atrial myosin isoform, we were able to identify the atrial myosin variants, to ~ classify the atrial fibers according to their myosin content, and to quantify the fiber-type distribution within the different regions in normal and diseased hearts. In the present work, we use three sets of monoclonal antibodies specific for ct, 13, and fl' ventricular myosin heavy chain isoforms, to study myosin dispersion and distribution within the ventricles of three normal and six diseased human hearts.…”

Heterogeneity of beta-type myosin isozymes in the human heart and regulational mechanisms in their expression. Immunohistochemical study using monoclonal antibodies.

“…Their distribution in normal human hearts and redistribution in pressureoverloaded atria were characteristic to p3-type myosin isozyme (10,31 In adult human hearts, HCa was expressed in almost all atrial myofibers and in a few ventricular myofibers. In contrast, #I and #2 might coexist in all ventricular myofibers and also exist in some myofibers of the atrium, where, however, they were not necessarily expressed simultaneously in individual myofibers.…”