References of "Schulte, Hagen D."
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See detailA molecular mechanism improving the contractile state in human myocardial hypertrophy.
Ritter, Oliver; Bottez, Nico; Burkard, Natalie et al

in Experimental and Clinical Cardiology (2002), 7(2-3), 151-7

BACKGROUND: Various molecular mechanisms are operative in altering the sarcomeric function of the heart under increased hemodynamic workload. Expression of the atrial isoform (ALC-1) of the essential ... [more ▼]

BACKGROUND: Various molecular mechanisms are operative in altering the sarcomeric function of the heart under increased hemodynamic workload. Expression of the atrial isoform (ALC-1) of the essential myosin light chain, a shift from alpha-myosin heavy chain (MHC) to beta-MHC, increased phosphorylation of the regulatory myosin light chains and increased troponin I (TnI) phosphorylation have been reported to modulate cardiac contractility in rodents. METHODS: TO ASSESS A POSSIBLE CONTRIBUTION OF THESE SARCOMERIC PROTEINS TO CARDIAC PERFORMANCE IN HUMAN MYOCARDIAL HYPERTROPHY, TWO DIFFERENT FORMS OF CARDIAC HYPERTROPHY WERE INVESTIGATED: 19 patients with hypertropic obstructive cardiomyopathy (HOCM) and 13 patients with aortic stenosis (AS) with marked left ventricular hypertrophy and normal systolic function. RESULTS: There was no change in MHC gene expression, regulatory myosin light chain or TnI phosphorylation status in normal heart (NH), HOCM and AS patients. However, patients with hypertrophied myocardium expressed ALC-1 that was not detectable in NH. ALC-1 protein expression correlated positively with the left ventricular ejection fraction. In patients with hypertrophied myocardium, there was a mean ALC-1 protein expression of 12.7+/-3% (range 3.6% to 32%). CONCLUSION: In humans, ALC-1 expression is in vivo a powerful molecular mechanism of the sarcomere to maintain or improve myocardial contractility under increased hemodynamic demands. [less ▲]

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See detailCalcineurin in human heart hypertrophy.
Ritter, Oliver; Hack, Susanne; Schuh, Kai et al

in Circulation (2002), 105(19), 2265-9

BACKGROUND: In animal models, increased signaling through the calcineurin pathway has been shown to be sufficient for the development of cardiac hypertrophy. Calcineurin activity has been reported to be ... [more ▼]

BACKGROUND: In animal models, increased signaling through the calcineurin pathway has been shown to be sufficient for the development of cardiac hypertrophy. Calcineurin activity has been reported to be elevated in the myocardium of patients with congestive heart failure. In contrast, few data are available about calcineurin activity in patients with pressure overload or cardiomyopathic hypertrophy who are not in cardiac failure. METHODS AND RESULTS: We investigated calcineurin activity and protein expression in 2 different forms of cardiac hypertrophy: hypertrophic obstructive cardiomyopathy (HOCM) and aortic stenosis (AS). We found that the C-terminus of calcineurin A protein containing the autoinhibitory domain was less abundant in myocardial hypertrophy than in normal heart, which suggests the possibility of proteolysis. No new splice variants could be detected by reverse-transcription polymerase chain reaction. This resulted in a significant elevation of calcineurin enzymatic activity in HOCM and AS compared with 6 normal hearts. Increased calcineurin phosphatase activity caused increased migration of NF-AT2 (nuclear factor of activated T cells 2) in SDS-PAGE compatible with pronounced NF-AT dephosphorylation in hypertrophied myocardial tissue. CONCLUSIONS: Hypertrophy in HOCM and AS without heart failure is characterized by a significant increase in calcineurin activity. This might occur by (partial) proteolysis of the calcineurin A C-terminus containing the autoinhibitory domain. Increased calcineurin activity has functional relevance, as shown by altered NF-AT phosphorylation state. Although hypertrophy in AS and HOCM may be initiated by different upstream triggers (internal versus external fiber overload), in both cases, there is activation of calcineurin, which suggests an involvement of this pathway in the pathogenesis of human cardiac hypertrophy. [less ▲]

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