Cardiac myosin autoantibodies from patients with dilated cardiomyopathy caused greater inhibition of myocyte contraction compared to antibodies from ischemic heart disease patients (P=0.004).
Do human cardiac myosin autoantibodies from patients with dilated cardiomyopathy impair myocyte contractility in isolated rat ventricular myocytes?
Cardiac myosin autoantibodies from patients with dilated cardiomyopathy directly impair myocyte contractility and alter calcium handling, suggesting a pathogenic role in clinical DCM.
p-value: p=0.004
ABSTRACT 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)
Warraich et al. (Fri,) conducted a other in Dilated cardiomyopathy and ischemic heart disease (n=38). Cardiac myosin autoantibodies from DCM patients vs. Cardiac myosin autoantibodies from IHD patients was evaluated on Inhibition of contraction in isolated myocytes (p=0.004). Cardiac myosin autoantibodies from patients with dilated cardiomyopathy caused greater inhibition of myocyte contraction compared to antibodies from ischemic heart disease patients (P=0.004).
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