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001-es BibID:	BIBFORM010415
Első szerző:	Borbély Attila (kardiológus)
Cím:	Hypophosphorylation of the Stiff N2B titin isoform raises cardiomyocyte resting tension in failing human myocardium / Borbely, A., Falcao-Pires, I., van Heerebeek, L., Hamdani, N., Edes, I., Gavina, C., Leite-Moreira, A. F., Bronzwaer, J. G. F., Papp, Z., van der Velden, J., Stienen, G. J. M., Paulus, W. J.
Dátum:	2009
ISSN:	1524-4571 (Electronic)
Megjegyzések:	High diastolic stiffness of failing myocardium results from interstitial fibrosis and elevated resting tension (F(passive)) of cardiomyocytes. A shift in titin isoform expression from N2BA to N2B isoform, lower overall phosphorylation of titin, and a shift in titin phosphorylation from N2B to N2BA isoform can raise F(passive) of cardiomyocytes. In left ventricular biopsies of heart failure (HF) patients, aortic stenosis (AS) patients, and controls (CON), we therefore related F(passive) of isolated cardiomyocytes to expression of titin isoforms and to phosphorylation of titin and titin isoforms. Biopsies were procured by transvascular technique (44 HF, 3 CON), perioperatively (25 AS, 4 CON), or from explanted hearts (4 HF, 8 CON). None had coronary artery disease. Isolated, permeabilized cardiomyocytes were stretched to 2.2-microm sarcomere length to measure F(passive). Expression and phosphorylation of titin isoforms were analyzed using gel electrophoresis with ProQ Diamond and SYPRO Ruby stains and reported as ratio of titin (N2BA/N2B) or of phosphorylated titin (P-N2BA/P-N2B) isoforms. F(passive) was higher in HF (6.1+/-0.4 kN/m(2)) than in CON (2.3+/-0.3 kN/m(2); P<0.01) or in AS (2.2+/-0.2 kN/m(2); P<0.001). Titin isoform expression differed between HF (N2BA/N2B=0.73+/-0.06) and CON (N2BA/N2B=0.39+/-0.05; P<0.001) and was comparable in HF and AS (N2BA/N2B=0.59+/-0.06). Overall titin phosphorylation was also comparable in HF and AS, but relative phosphorylation of the stiff N2B titin isoform was significantly lower in HF (P-N2BA/P-N2B=0.77+/-0.05) than in AS (P-N2BA/P-N2B=0.54+/-0.05; P<0.01). Relative hypophosphorylation of the stiff N2B titin isoform is a novel mechanism responsible for raised F(passive) of human HF cardiomyocytes.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Aged Biopsy Elasticity Female Heart Failure Humans Male Middle Aged Muscle Proteins Myocardium Myocytes, Cardiac Phosphorylation Protein Isoforms Protein Kinases Sarcomeres
Megjelenés:	Circulation Research. - 104 : 6 (2009), p. 780-786. -
További szerzők:	Falcao-Pires, Ines Heerebeek, Loek, van Hamdani, Nazha Édes István (1952-) (kardiológus) Gavina, Cristina Leite-Moreira, Adelino F. Bronzwaer, Jean G. F. Papp Zoltán (1965-) (kardiológus, élettanász) Velden, Jolanda, van der Stienen, Ger J. M. Paulus, Walter J.
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001-es BibID:	BIBFORM023507
Első szerző:	Falcao-Pires, Ines
Cím:	Diabetes Mellitus Worsens Diastolic Left Ventricular Dysfunction in Aortic Stenosis Through Altered Myocardial Structure and Cardiomyocyte Stiffness / Falcao-Pires, I., Hamdani, N., Borbely, A., Gavina, C., Schalkwijk, C. G., van der Velden, J., van Heerebeek, L., Stienen, G. J. M., Niessen, H. W. M., Leite-Moreira, A. F., Paulus, W. J.
Dátum:	2011
ISSN:	0009-7322
Megjegyzések:	Aortic stenosis (AS) and diabetes mellitus (DM) are frequent comorbidities in aging populations. In heart failure, DM worsens diastolic left ventricular (LV) dysfunction, thereby adversely affecting symptoms and prognosis. Effects of DM on diastolic LV function were therefore assessed in aortic stenosis, and underlying myocardial mechanisms were identified. Methods and Results-Patients referred for aortic valve replacement were subdivided into patients with AS and no DM (AS; n=46) and patients with AS and DM (AS-DM; n=16). Preoperative Doppler echocardiography and hemodynamics were implemented with perioperative LV biopsies. Histomorphometry and immunohistochemistry quantified myocardial collagen volume fraction and myocardial advanced glycation end product deposition. Isolated cardiomyocytes were stretched to 2.2-gamma m sarcomere length to measure resting tension (Fpassive). Expression and phosphorylation of titin isoforms were analyzed with gel electrophoresis with ProQ Diamond and SYPRO Ruby stains. Reduced LV end-diastolic distensibility in AS-DM was evident from higher LV end-diastolic pressure (21±1 mm Hg for AS versus 28±4 mm Hg for AS-DM; P=0.04) at comparable LV end-diastolic volume index and attributed to higher myocardial collagen volume fraction (AS, 12.9±1.1% versus AS-DM, 18.2±2.6%; P<0.001), more advanced glycation end product deposition in arterioles, venules, and capillaries (AS, 14.4±2.1 score per 1 mm2 versus AS-DM, 31.4±6.1 score per 1 mm2; P=0.03), and higher Fpassive (AS, 3.5±1.7 kN/m2 versus AS-DM, 5.1±0.7 kN/m2; P=0.04). Significant hypophosphorylation of the stiff N2B titin isoform in AS-DM explained the higher Fpassive and normalization of Fpassive after in vitro treatment with protein kinase A. Conclusions-Worse diastolic LV dysfunction in AS-DM predisposes to heart failure and results from more myocardial fibrosis, more intramyocardial vascular advanced glycation end product deposition, and higher cardiomyocyte Fpassive, which was related to hypophosphorylation of the N2B titin isoform.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban aortic valve stenosis myocytes cardiac diabetes mellitus diastole fibrosis titin myofilamentary proteins
Megjelenés:	Circulation. - 124 : 10 (2011), p. 1151-1159. -
További szerzők:	Hamdani, Nazha Borbély Attila (1978-) (kardiológus) Gavina, Cristina Schalkwijk, Casper G. Velden, Jolanda, van der Heerebeek, Loek, van Stienen, Ger J. M. Niessen, Hans W. M. Leite-Moreira, Adelino F. Paulus, Walter J.
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001-es BibID:	BIBFORM003763
Első szerző:	Paulus, Walter J.
Cím:	How to diagnose diastolic heart failure : a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology / Paulus, W. J., Tschope, C., Sanderson, J. E., Rusconi, C., Flachskampf, F. A., Rademakers, F. E., Marino, P., Smiseth, O. A., De Keulenaer, G., Leite-Moreira, A. F., Borbely, A., Edes, I., Handoko, M. L., Heymans, S., Pezzali, N., Pieske, B., Dickstein, K., Fraser, A. G., Brutsaert, D. L.
Dátum:	2007
Megjegyzések:	Diastolic heart failure (DHF) currently accounts for more than 50% of all heart failure patients. DHF is also referred to as heart failure with normal left ventricular (LV) ejection fraction (HFNEF) to indicate that HFNEF could be a precursor of heart failure with reduced LVEF. Because of improved cardiac imaging and because of widespread clinical use of plasma levels of natriuretic peptides, diagnostic criteria for HFNEF needed to be updated. The diagnosis of HFNEF requires the following conditions to be satisfied: (i) signs or symptoms of heart failure; (ii) normal or mildly abnormal systolic LV function; (iii) evidence of diastolic LV dysfunction. Normal or mildly abnormal systolic LV function implies both an LVEF > 50% and an LV end-diastolic volume index (LVEDVI) <97 mL/m(2). Diagnostic evidence of diastolic LV dysfunction can be obtained invasively (LV end-diastolic pressure >16 mmHg or mean pulmonary capillary wedge pressure >12 mmHg) or non-invasively by tissue Doppler (TD) (E/E' > 15). If TD yields an E/E' ratio suggestive of diastolic LV dysfunction (15 > E/E' > 8), additional non-invasive investigations are required for diagnostic evidence of diastolic LV dysfunction. These can consist of blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, electrocardiographic evidence of atrial fibrillation, or plasma levels of natriuretic peptides. If plasma levels of natriuretic peptides are elevated, diagnostic evidence of diastolic LV dysfunction also requires additional non-invasive investigations such as TD, blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, or electrocardiographic evidence of atrial fibrillation. A similar strategy with focus on a high negative predictive value of successive investigations is proposed for the exclusion of HFNEF in patients with breathlessness and no signs of congestion. The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies for HFNEF
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Biological Markers blood Consensus diagnosis Diagnosis,Differential Diastole Echocardiography Echocardiography,Doppler Heart Failure Humans methods Natriuretic Peptides physiology Stroke Volume therapy ultrasonography
Megjelenés:	European Heart Journal. - 28 : 20 (2007), p. 2539-2550. -
További szerzők:	Tschöpe, Carsten Sanderson, John E. Rusconi, Cesare Flachskampf, Frank A. Rademakers, Frank E. Marino, Paolo Smiseth, Otto A. De Keulenaer, Gilles Leite-Moreira, Adelino F. Borbély Attila (1978-) (kardiológus) Édes István (1952-) (kardiológus) Handoko, Martin Louis Heymans, Stephane Pezzali, Natalia Pieske, Burkert Dickstein, Kenneth Fraser, Alan G. Brutsaert, Dirk L.
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