[The extracellular matrix and cytoskeleton of the myocardium in cardiac inflammatory reaction].
The cardiac cytoskeleton and the extracellular matrix play an essential role for maintaining cellular integrity and function of the myocardium. The network of microtubules and intermediate filaments are disrupted by the inflammatory reaction which depends on resident cells (myocytes, fibroblasts, endothel cells) and on systemic cells (granulocytes, macrophages, monocytes, lymphocytes). Changes in the cardiac cytoskeleton and the extracellular matrix may affect contractile function, since the cytoskeleton organizes the intra- and intercellular architecture. The inflammation in heart disease and the induction of fibrosis are mediated by cytokines and growth factors derived from fibroblast activation and from the B- and T-cell activity. A possible connecting link for the induction of fibrosis is the presentation of the myocardial antigens to the immune system and its subsequent cellular and humoral autoreactive response (Figure 1). Different autoantibodies to sarcolemmal and myolemmal antigens, to laminin, to extracellular matrix proteins, to the collagens and to myofibrils were demonstrated both in endomyocardial biopsy and as circulating autoantibodies in the peripheral blood. The pathophysiological role of the cytoskeleton and the extracellular matrix are well defined for beta-tubulin, fibronectin, laminin, desmin, vimentin, vinculin and collagen: beta-tubulin is increased or altered in dilated cardiomyopathy (DCM). Fibronectin appears in irregular forms in DCM as well. Ultrastructural analysis showed an increased content of laminin in basement membranes. In addition anti-laminin antibodies were found in 73% of patients with myocarditis and in 78% of patients with DCM. Desmin (z-bands) are partly destroyed in DCM. Anti-desmin antibody titers as indicators of a possible secondary immune response are found high in patients with acute myocarditis declining during reconvalescence and are also elevated in DCM. The vimentin of the endothelial cells and the vinculin of the sarcolemmal membrane and the intercalated discs have been demonstrated to be irregularly shaped and increased in content in DCM whereas in myocarditis their appearance and content is still unknown. The intracellular content of collagen type 5 is increased in DCM and in myocarditis. The presence of autoantibodies to components of the cytoskeleton and the extracellular matrix in myocarditis and perimyocarditis is well-described. Antibodies to the myolemma and the sarcolemma are found in almost all patients with perimyocarditis in the serum or bound in the biopsy. Some of them have been known cytolytic in vitro to isolated heart cells. In pericarditis a shift to antibodies to the extracellular matrix, collagen and intermediate filaments is observed among the circulating antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)
Wilke
A
A
Abteilung Kardiologie, Philipps-Universität Marburg.
Schönian
U
U
Herzum
M
M
Hengstenberg
C
C
Hufnagel
G
G
Brilla
C G
CG
Maisch
B
B
D001323:Autoantibodies / Q000032:analysis; D003599:Cytoskeleton / Q000276:immunology / Q000473:pathology*; D004697:Endocarditis, Bacterial / Q000276:immunology / Q000473:pathology; D005109:Extracellular Matrix / Q000276:immunology / Q000473:pathology*; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D009205:Myocarditis / Q000276:immunology / Q000473:pathology*; D009206:Myocardium / Q000276:immunology / Q000473:pathology*
D001323:Autoantibodies; D018836:Inflammation Mediators
Extrazelluläre Matrix und Zytoskelett des Myokards bei kardialer Entzündungsreaktion.