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Human cardiac myosin autoantibodies impair myocyte contractility: a cause‐and‐effect relationship
Author(s) -
Warraich Rahat S.,
Griffiths Elinor,
Falconar Andrew,
Pabbathi Vijay,
Bell Chris,
Angelini Gianni,
Suleiman M.Saadeh,
Yacoub Magdi H.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3001com
Subject(s) - contractility , myocyte , medicine , autoantibody , contraction (grammar) , dilated cardiomyopathy , cardiology , myosin , endocrinology , diastole , cardiomyopathy , cardiac myocyte , heart failure , biology , antibody , biophysics , immunology , blood pressure
The functional relevance of autoanti‐bodies (Abs) against cardiac myosin (CM) in clinical idiopathic dilated cardiomyopathy (DCM) remains controversial. The study sought to determine effects of human Abs affinity‐purified (AF) by immunoaffinity column chromotography on excitation‐contraction coupling in isolated myocytes. Effects of CM‐Abs from heart failure patients with DCM ( n =19) and ischemic heart disease (IHD, n =19) on contractility, L‐type Ca 2+ current, and Ca 2+ transients in continuously perfused rat ventricular myocytes were studied. Immunofluorescence studies using confocal microscopy were carried out to determine whether Abs were internalized. AF‐Abs from either group did not differ in IgG titer but differed in their elution profiles. The IgG3 subclass response was higher in AF fractions from DCM (21%) than IHD (5%) patients. The Abs reduced the capacity of field‐stimulated myocytes to contract in a dose‐dependent manner. Inhibition of contraction, as a percentage of untreated cells, was greater with DCM than IHD‐Abs ( P =0.004), and the effect was independent of Ab titer. An increase in frequency of the beating myocytes (0.2 to 3.0 Hz) raised peak systolic and diastolic levels of [Ca 2 + ] i of cells treated with DCM but not IHD‐Abs ( P <0.005). The AF‐Abs were not internalized by myocytes and had no effect on L‐type Ca 2+ currents. The altered sensitivity of the myofilaments to [Ca 2 + ] i by CM‐Abs may represent a potential mechanism of autoantibody‐mediated impairment in clinical DCM.‐Warraich, R. S., Griffiths, E., Falconar, A., Pabbathi, V., Bell, C., Angelini, G., Suleiman, M.‐S., Yacoub, M. H. Human cardiac myosin autoantibodies impair myocyte contractility: a cause‐and‐effect relationship. FASEB J. 20, 651–660 (2006)