We have previously shown that physical conditioning in the rat improves cardiac mechanics and biochemistry and normalizes the cardiac contractile protein abnormalities associated with renovascular hypertension. Since chronic adrenergic stimulation with dobutamine simulates some aspects of physical conditioning, this study was undertaken to investigate the effects of chronic dobutamine administr...

Human cardiac myosin isolated from operatively obtained samples of ventricular septum and left ventricular free wall of subjects with asymmetric septal hypertrophy (ASH) was compared, with respect to structural and enzymatic properties, to myosin isolated from hearts of subjects without heart disease. The following parameters were studied: (1) activation of myosin ATPase activity by K+-EDTA and...

The participation of cardiac myosin hinge in contractility was investigated by in vitro motility and ATPase assays and by measurements of sarcomere shortening. The effect on contractile activity was analyzed using an antibody directed against a 20-amino acid peptide within the hinge region of myosin. This antibody bound specifically at the hinge at a distance of 55 nm from the S1/S2 junction, w...

The sarcomeric proteins and organization of cardiac myofibrils appeared intact in multiple unrelated patients with hypertrophic cardiomyopathy. In two subjects demonstrating the missense mutation at position 403 (Arg to Gln) in the beta-myosin heavy chain gene, total myosin and immunoreactive beta-myosin heavy chain levels were similar to those found in other patients with hypertrophic cardiomy...

T cells constitute the pathogenic effector cell population in autoimmune myocarditis in BALB/c mice. Using mice rendered deficient for B cells by a targeted disruption to the IgM transmembrane domain or by treatment with anti-IgM Ab from birth, we asked whether B cells are a critical APC in the induction of autoimmune myocarditis. B cell-deficient mice immunized with cardiac myosin develop myoc...

The essential myosin light chain (ELC) is involved in modulation of force generation of myosin motors and cardiac contraction, while its mechanism of action remains elusive. We hypothesized that ELC could modulate myosin stiffness which subsequently determines its force production and cardiac contraction. Therefore, we generated heterologous transgenic mouse (TgM) strains with cardiomyocyte-spe...

Background. Immunization with cardiac myosin induces experimental autoimmune heart disease in genetically predisposed mice. These mice produce heart-specific autoantibodies, some of which are directed against the cardiac myosin isoform. Methods and Results. We have reported the presence of circulating heart-specific autoantibodies in 26% of patients with idiopathic dilated cardiomyopathy (DCM) ...

Chagas disease cardiomyopathy (CCC) is one of the few examples of post-infectious autoimmunity, where infectious episodes with an established pathogen, the protozoan parasite Trypanosoma cruzi, clearly triggers molecular mimicry-related target organ immune damage. CD4+ T-cell clones infiltrating hearts from CCC patients cross-reactively recognize human cardiac myosin, the major heart protein, a...