Low Myocardial Protein Kinase G Activity in Heart Failure With Preserved Ejection Fraction
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- 14 August 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 126 (7), 830-839
- https://doi.org/10.1161/circulationaha.111.076075
Abstract
Background—: Prominent features of myocardial remodeling in heart failure with preserved ejection fraction (HFPEF) are high cardiomyocyte resting tension (F passive ) and cardiomyocyte hypertrophy. In experimental models, both reacted favorably to raised protein kinase G (PKG) activity. The present study assessed myocardial PKG activity, its downstream effects on cardiomyocyte F passive and cardiomyocyte diameter, and its upstream control by cyclic guanosine monophosphate (cGMP), nitrosative/oxidative stress, and brain natriuretic peptide (BNP). To discern altered control of myocardial remodeling by PKG, HFPEF was compared with aortic stenosis and HF with reduced EF (HFREF). Methods and Results—: Patients with HFPEF (n=36), AS (n=67), and HFREF (n=43) were free of coronary artery disease. More HFPEF patients were obese ( P P passive was measured in cardiomyocytes before and after PKG administration. Myocardial homogenates were used for assessment of PKG activity, cGMP concentration, proBNP-108 expression, and nitrotyrosine expression, a measure of nitrosative/oxidative stress. Additional quantitative immunohistochemical analysis was performed for PKG activity and nitrotyrosine expression. Lower PKG activity in HFPEF than in aortic stenosis ( P P passive ( P P P passive in HFPEF was corrected by in vitro PKG administration. Conclusions—: Low myocardial PKG activity in HFPEF was associated with raised cardiomyocyte F passive and was related to increased myocardial nitrosative/oxidative stress. The latter was probably induced by the high prevalence in HFPEF of metabolic comorbidities. Correction of myocardial PKG activity could be a target for specific HFPEF treatment.Keywords
This publication has 45 references indexed in Scilit:
- Sildenafil and B-Type Natriuretic Peptide Acutely Phosphorylate Titin and Improve Diastolic Distensibility In VivoCell Metabolism, 2011
- Tachycardia-Induced Diastolic Dysfunction and Resting Tone in Myocardium From Patients With a Normal Ejection FractionJournal of the American College of Cardiology, 2011
- Body Mass Index and Adverse Cardiovascular Outcomes in Heart Failure Patients With Preserved Ejection FractionCirculation: Heart Failure, 2011
- Effect of Obesity and Overweight on Left Ventricular Diastolic FunctionJournal of the American College of Cardiology, 2011
- Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatmentEuropean Heart Journal, 2010
- Myocardial Remodeling Is Controlled by Myocyte-Targeted Gene Regulation of Phosphodiesterase Type 5Journal of the American College of Cardiology, 2010
- Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytesProceedings of the National Academy of Sciences of the United States of America, 2010
- Uncoupled Cardiac Nitric Oxide Synthase Mediates Diastolic DysfunctionCirculation, 2010
- Modulation of Titin-Based Stiffness by Disulfide Bonding in the Cardiac Titin N2-B Unique SequenceBiophysical Journal, 2009
- Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failureEuropean Heart Journal, 2008