Burkert Pieske - Academia.edu (original) (raw)

Papers by Burkert Pieske

Circulation, Oct 31, 2007

Biophys J, 2011

Biological membranes remodel in lipid pore formation, fusion, endocytosis and other processes. Tr... more Biological membranes remodel in lipid pore formation, fusion, endocytosis and other processes. Traditionally, continuum membrane mechanics has been used to describe the physics of these remodelings. Membrane mechanics is a conservative, equilibrium theory and so cannot, a priori, describe the time course, flows and dissipations of a real system. Over the past few decades, physical scientists and mathematicians have developed global multi-physics field equations that describe the time course of processes for condensed matter in a thermodynamically consistent way. We use these equations to describe the membrane during lipid bilayer membrane remodelings. We analyze the vesicle membrane and its lipid layers as a bulk continuum variable in a Hamiltonian. The Hamiltonian includes the surface tension and curvature effects of the classical Helfrich model. The representations are, however, more flexible and can readily account for multicomponent systems, inhomogeneities, and changes in topology. Coupling the Hamiltonian to the motion of the aqueous medium with Rayleigh dissipation leads to a complicated, self-consistent system of partial differential equations that is solved numerically. Numerical schemes, designed specifically for this field theory, provide the position, velocity and forces of the fluid-vesicle system at each point in space and time. Classical models assume a specific shape for the vesicle (e.g., a sphere). The assumed shape will occur in the real world, however, only if it is a self-consistent solution of the equations. Our calculations yield values of all key variables and energies over time-the shape is an output. Movies that precisely illustrate the time evolution of the membrane configuration are generated. Changes over time are appreciated visually without reference to the equations-or even to the physics-of the remodeling processes.

Journal of Molecular and Cellular Cardiology, 2016

AMP-activated protein kinase (Ampk) regulates myocardial energy metabolism and plays a crucial ro... more AMP-activated protein kinase (Ampk) regulates myocardial energy metabolism and plays a crucial role in the response to cell stress. In the failing heart, an isoform shift of the predominant Ampkα2 to the Ampkα1 was observed. The present study explored possible isoform specific effects of Ampkα1 in cardiomyocytes. To this end, experiments were performed in HL-1 cardiomyocytes, as well as in Ampkα1-deficient and corresponding wild-type mice and mice following AAV9-mediated cardiac overexpression of constitutively active Ampkα1. As a result, in HL-1 cardiomyocytes, overexpression of constitutively active Ampkα1 increased the phosphorylation of Pkcζ. Constitutively active Ampkα1 further increased AP-1-dependent transcriptional activity and mRNA expression of the AP-1 target genes c-Fos, Il6 and Ncx1, effects blunted by Pkcζ silencing. In HL-1 cardiomyocytes, angiotensin-II activated AP-1, an effect blunted by silencing of Ampkα1 and Pkcζ, but not of Ampkα2. In wild-type mice, angiotensin-II infusion increased cardiac Ampkα1 and cardiac Pkcζ protein levels, as well as c-Fos, Il6 and Ncx1 mRNA expression, effects blunted in Ampkα1-deficient mice. Pressure overload by transverse aortic constriction (TAC) similarly increased cardiac Ampkα1 and Pkcζ abundance as well as c-Fos, Il6 and Ncx1 mRNA expression, effects again blunted in Ampkα1-deficient mice. AAV9-mediated cardiac overexpression of constitutively active Ampkα1 increased Pkcζ protein abundance and the mRNA expression of c-Fos, Il6 and Ncx1 in cardiac tissue. In conclusion, Ampkα1 promotes myocardial AP-1 activation in a Pkcζ-dependent manner and thus contributes to cardiac stress signaling.

Circulation, Nov 25, 2014

Circulation, Nov 20, 2012

Circulation, Nov 25, 2014

American Journal of Physiology Heart and Circulatory Physiology, Apr 1, 1998

Effects of left ventricular hypertrophy on force and Ca 2ϩ handling in isolated rat myocardium. A... more Effects of left ventricular hypertrophy on force and Ca 2ϩ handling in isolated rat myocardium. Am. J. Physiol. 274 (Heart Circ. Physiol. 43): H1361-H1370, 1998.-To study the effect of left ventricular (LV) hypertrophy on force and Ca 2ϩ handling in isolated rat myocardium, LV hypertrophy was induced in rats by banding of the abdominal aorta. After 16 wk, arterial pressure was assessed by catheterization. LV trabeculae were isolated and loaded with indo 1 salt by iontophoretic injection. Isometric force and intracellular free Ca 2ϩ concentration ([Ca 2ϩ ] i ) were measured at stimulation frequencies between 0.25 and 3 Hz and rest intervals between 2 and 240 s. Sarcoplasmic reticulum (SR) Ca 2ϩ content was also investigated using rapid cooling contractures (RCC). Systolic and diastolic pressure as well as heart weight-to-body weight ratios were significantly elevated in banded compared with control animals (167 vs. 117 mmHg, 108 vs. 83 mmHg, and 4.6 vs. 4.0 mg/g, respectively). At high frequencies, twitch relaxation and [Ca 2ϩ ] i decline rates were significantly slower in banded compared with control rats, and diastolic [Ca 2ϩ ] i was higher in the banded rat muscles (at 3 Hz, force half-time ϭ 83 vs. 68 ms; time constant of [Ca 2ϩ ] i decline ϭ 208 vs. 118 ms; and diastolic [Ca 2ϩ ] i ϭ 505 vs. 353 nM). These differences could not be ascribed to altered Na ϩ /Ca 2ϩ exchange, since twitch relaxation and Ca 2ϩ handling were not different between groups in the presence of caffeine (or cyclopiazonic acid plus ryanodine), where relaxation depends primarily on Na ϩ /Ca 2ϩ exchange. After long rest intervals (Ն120 s), control rats showed a significant rest potentiation of force and Ca 2ϩ transients, whereas banded rats did not. In addition, RCC amplitudes increased with rest in control but were unaltered in banded rats. In summary, pressure-overload hypertrophy was associated with slower twitch relaxation and [Ca 2ϩ ] i decline but also with blunted rest potentiation of twitches and SR Ca 2ϩ content of LV trabeculae. The decrease in SR Ca 2ϩ -ATPase function in banded rats may contribute to the observed diastolic dysfunction associated with pressure-overload hypertrophy.

Circulation, Nov 20, 2012

Circulation, Nov 23, 2010

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, Jan 21, 2015

Clinical Investigation, 2012

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an... more Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network.

Frontiers in physiology, 2014

Dyssynchronous local Ca release within individual cardiac myocytes has been linked to cellular co... more Dyssynchronous local Ca release within individual cardiac myocytes has been linked to cellular contractile dysfunction. Differences in Ca kinetics in adjacent cells may also provide a substrate for inefficient contraction and arrhythmias. In a new approach we quantify variation in local Ca transients between adjacent myocytes in the whole heart. Langendorff-perfused mouse hearts were loaded with Fluo-8 AM to detect Ca and Di-4-ANEPPS to visualize cell membranes. A spinning disc confocal microscope with a fast camera allowed us to record Ca signals within an area of 465 μm by 315 μm with an acquisition speed of 55 fps. Images from multiple transients recorded at steady state were registered to their time point in the cardiac cycle to restore averaged local Ca transients with a higher temporal resolution. Local Ca transients within and between adjacent myocytes were compared with regard to amplitude, time to peak and decay at steady state stimulation (250 ms cycle length). Image regis...

European journal of preventive cardiology, 2014

Heart failure with preserved left ventricular ejection fraction (HFpEF) currently affects more th... more Heart failure with preserved left ventricular ejection fraction (HFpEF) currently affects more than seven million Europeans and is the only cardiovascular disease increasing in prevalence and incidence. No pharmacological agent has yet been shown to improve symptoms or prognosis. The most promising way to improve pathophysiology and deprived exercise-tolerance in HFpEF patients seems to be exercise training, but the optimal approach and dose of exercise is still unknown. The major objective of the optimising exercise training in prevention and treatment of diastolic heart failure study (OptimEx-CLIN) is to define the optimal dose of exercise training in patients with HFpEF. In order to optimise adherence, supervision and economic aspects of exercise training a novel telemedical approach will be introduced and investigated. In a prospective randomised multi-centre study, 180 patients with stable symptomatic HFpEF will be randomised (1:1:1) to moderate intensity continuous training, h...

Journal of Cardiac Failure, 2014

European heart journal, Jan 21, 2014

Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection f... more Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall...

Journal of the American College of Cardiology, Jan 7, 2014

Circulation, Oct 31, 2007

Biophys J, 2011

Biological membranes remodel in lipid pore formation, fusion, endocytosis and other processes. Tr... more Biological membranes remodel in lipid pore formation, fusion, endocytosis and other processes. Traditionally, continuum membrane mechanics has been used to describe the physics of these remodelings. Membrane mechanics is a conservative, equilibrium theory and so cannot, a priori, describe the time course, flows and dissipations of a real system. Over the past few decades, physical scientists and mathematicians have developed global multi-physics field equations that describe the time course of processes for condensed matter in a thermodynamically consistent way. We use these equations to describe the membrane during lipid bilayer membrane remodelings. We analyze the vesicle membrane and its lipid layers as a bulk continuum variable in a Hamiltonian. The Hamiltonian includes the surface tension and curvature effects of the classical Helfrich model. The representations are, however, more flexible and can readily account for multicomponent systems, inhomogeneities, and changes in topology. Coupling the Hamiltonian to the motion of the aqueous medium with Rayleigh dissipation leads to a complicated, self-consistent system of partial differential equations that is solved numerically. Numerical schemes, designed specifically for this field theory, provide the position, velocity and forces of the fluid-vesicle system at each point in space and time. Classical models assume a specific shape for the vesicle (e.g., a sphere). The assumed shape will occur in the real world, however, only if it is a self-consistent solution of the equations. Our calculations yield values of all key variables and energies over time-the shape is an output. Movies that precisely illustrate the time evolution of the membrane configuration are generated. Changes over time are appreciated visually without reference to the equations-or even to the physics-of the remodeling processes.

Journal of Molecular and Cellular Cardiology, 2016

AMP-activated protein kinase (Ampk) regulates myocardial energy metabolism and plays a crucial ro... more AMP-activated protein kinase (Ampk) regulates myocardial energy metabolism and plays a crucial role in the response to cell stress. In the failing heart, an isoform shift of the predominant Ampkα2 to the Ampkα1 was observed. The present study explored possible isoform specific effects of Ampkα1 in cardiomyocytes. To this end, experiments were performed in HL-1 cardiomyocytes, as well as in Ampkα1-deficient and corresponding wild-type mice and mice following AAV9-mediated cardiac overexpression of constitutively active Ampkα1. As a result, in HL-1 cardiomyocytes, overexpression of constitutively active Ampkα1 increased the phosphorylation of Pkcζ. Constitutively active Ampkα1 further increased AP-1-dependent transcriptional activity and mRNA expression of the AP-1 target genes c-Fos, Il6 and Ncx1, effects blunted by Pkcζ silencing. In HL-1 cardiomyocytes, angiotensin-II activated AP-1, an effect blunted by silencing of Ampkα1 and Pkcζ, but not of Ampkα2. In wild-type mice, angiotensin-II infusion increased cardiac Ampkα1 and cardiac Pkcζ protein levels, as well as c-Fos, Il6 and Ncx1 mRNA expression, effects blunted in Ampkα1-deficient mice. Pressure overload by transverse aortic constriction (TAC) similarly increased cardiac Ampkα1 and Pkcζ abundance as well as c-Fos, Il6 and Ncx1 mRNA expression, effects again blunted in Ampkα1-deficient mice. AAV9-mediated cardiac overexpression of constitutively active Ampkα1 increased Pkcζ protein abundance and the mRNA expression of c-Fos, Il6 and Ncx1 in cardiac tissue. In conclusion, Ampkα1 promotes myocardial AP-1 activation in a Pkcζ-dependent manner and thus contributes to cardiac stress signaling.

Circulation, Nov 25, 2014

Circulation, Nov 20, 2012

Circulation, Nov 25, 2014

American Journal of Physiology Heart and Circulatory Physiology, Apr 1, 1998

Effects of left ventricular hypertrophy on force and Ca 2ϩ handling in isolated rat myocardium. A... more Effects of left ventricular hypertrophy on force and Ca 2ϩ handling in isolated rat myocardium. Am. J. Physiol. 274 (Heart Circ. Physiol. 43): H1361-H1370, 1998.-To study the effect of left ventricular (LV) hypertrophy on force and Ca 2ϩ handling in isolated rat myocardium, LV hypertrophy was induced in rats by banding of the abdominal aorta. After 16 wk, arterial pressure was assessed by catheterization. LV trabeculae were isolated and loaded with indo 1 salt by iontophoretic injection. Isometric force and intracellular free Ca 2ϩ concentration ([Ca 2ϩ ] i ) were measured at stimulation frequencies between 0.25 and 3 Hz and rest intervals between 2 and 240 s. Sarcoplasmic reticulum (SR) Ca 2ϩ content was also investigated using rapid cooling contractures (RCC). Systolic and diastolic pressure as well as heart weight-to-body weight ratios were significantly elevated in banded compared with control animals (167 vs. 117 mmHg, 108 vs. 83 mmHg, and 4.6 vs. 4.0 mg/g, respectively). At high frequencies, twitch relaxation and [Ca 2ϩ ] i decline rates were significantly slower in banded compared with control rats, and diastolic [Ca 2ϩ ] i was higher in the banded rat muscles (at 3 Hz, force half-time ϭ 83 vs. 68 ms; time constant of [Ca 2ϩ ] i decline ϭ 208 vs. 118 ms; and diastolic [Ca 2ϩ ] i ϭ 505 vs. 353 nM). These differences could not be ascribed to altered Na ϩ /Ca 2ϩ exchange, since twitch relaxation and Ca 2ϩ handling were not different between groups in the presence of caffeine (or cyclopiazonic acid plus ryanodine), where relaxation depends primarily on Na ϩ /Ca 2ϩ exchange. After long rest intervals (Ն120 s), control rats showed a significant rest potentiation of force and Ca 2ϩ transients, whereas banded rats did not. In addition, RCC amplitudes increased with rest in control but were unaltered in banded rats. In summary, pressure-overload hypertrophy was associated with slower twitch relaxation and [Ca 2ϩ ] i decline but also with blunted rest potentiation of twitches and SR Ca 2ϩ content of LV trabeculae. The decrease in SR Ca 2ϩ -ATPase function in banded rats may contribute to the observed diastolic dysfunction associated with pressure-overload hypertrophy.

Circulation, Nov 20, 2012

Circulation, Nov 23, 2010

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, Jan 21, 2015

Clinical Investigation, 2012

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an... more Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network.

Frontiers in physiology, 2014

Dyssynchronous local Ca release within individual cardiac myocytes has been linked to cellular co... more Dyssynchronous local Ca release within individual cardiac myocytes has been linked to cellular contractile dysfunction. Differences in Ca kinetics in adjacent cells may also provide a substrate for inefficient contraction and arrhythmias. In a new approach we quantify variation in local Ca transients between adjacent myocytes in the whole heart. Langendorff-perfused mouse hearts were loaded with Fluo-8 AM to detect Ca and Di-4-ANEPPS to visualize cell membranes. A spinning disc confocal microscope with a fast camera allowed us to record Ca signals within an area of 465 μm by 315 μm with an acquisition speed of 55 fps. Images from multiple transients recorded at steady state were registered to their time point in the cardiac cycle to restore averaged local Ca transients with a higher temporal resolution. Local Ca transients within and between adjacent myocytes were compared with regard to amplitude, time to peak and decay at steady state stimulation (250 ms cycle length). Image regis...

European journal of preventive cardiology, 2014

Heart failure with preserved left ventricular ejection fraction (HFpEF) currently affects more th... more Heart failure with preserved left ventricular ejection fraction (HFpEF) currently affects more than seven million Europeans and is the only cardiovascular disease increasing in prevalence and incidence. No pharmacological agent has yet been shown to improve symptoms or prognosis. The most promising way to improve pathophysiology and deprived exercise-tolerance in HFpEF patients seems to be exercise training, but the optimal approach and dose of exercise is still unknown. The major objective of the optimising exercise training in prevention and treatment of diastolic heart failure study (OptimEx-CLIN) is to define the optimal dose of exercise training in patients with HFpEF. In order to optimise adherence, supervision and economic aspects of exercise training a novel telemedical approach will be introduced and investigated. In a prospective randomised multi-centre study, 180 patients with stable symptomatic HFpEF will be randomised (1:1:1) to moderate intensity continuous training, h...

Journal of Cardiac Failure, 2014

European heart journal, Jan 21, 2014

Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection f... more Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall...

Journal of the American College of Cardiology, Jan 7, 2014