Protein kinase G corrects high cardiomyocyte resting tension in diastolic heart failure.

• Type: Summary of Presentation in an International Conference
• Date: 2007

Authors

Hamdani N (Author) Other; Borbely A (Author) Other; Boontje NM (Author) Other; Edes I (Author) Other; Falcão-Pires I (Author) FMUP; Leite-Moreira AF (Author) FMUP; Stienen GJ (Author) Other; van der Velden J (Author) Other; Paulus WJ (Author) Other

Conference proceedings International

Title: Circulation

Initial page: II-708

80th Scientific Sessions of the American Heart Association

Orlando, FL, EUA, 04 a 07 de Novembro de 2007

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): Cardiomyocytes isolated from LV myocardium of diastolic heart failure (DHF) patients have high in-vitro resting tension (RT), which is corrected by administration of protein kinase A (PKA) and which contributes to in-vivo left ventricular (LV) diastolic stiffness. Treatment with nitric oxide donors or sildenafil, both of which raise myocardial protein kinase G (PKG) activity, improves in-vivo diastolic LV stiffness in humans and in experimental rodent models. In-vitro effect of PKG administration on RT of cardiomyocytes of DHF patients was therefore investigated. Cardiomyocytes were isolated from endomyocardial biopsies of DHF patients (n = 7), of aortic stenosis (AS) patients (n = 20) and of controls (CON) (n = 8). All patients were free of coronary artery disease and had no inflammatory infiltration in their biopsy. Cardiomyocytes were treated with Triton X-100, attached to a force transducer and stretched to a sarcomere length of 2.2 microm to measure RT before and after administration of PKG and PKA. Expression and phosphorylation of myosin binding protein C, troponin I (TnI), troponin T, desmin, myosin light chain 2, stiff N2B titin isoform and compliant N2BA titin isoform were analysed using gel electrophoresis with SYPRO Ruby and Pro-Q Diamond Phosphoprotein Stain. Baseline RT was higher in DHF than in AS or in CON and fell after administration of both PKG and PKA (Table). PKA had no effects on RT in AS or in CON. DHF had lower baseline phosphorylation of troponin I compared to AS (p < 0.05) and of the stiff N2B titin isoform compared to both AS (p < 0.05) and CON (p < 0.01). Conclusion: In vitro administration of PKG or PKA lowers the high RT of cardiomyocytes of DHF patients probably through correction of a phosphorylation deficit of troponin I or of the stiff N2B titin isoform. These observations support the clinical use of nitric oxide donors or of sildenafil for the treatment of high diastolic LV stiffness in DHF.

Language: English

Type (Professor's evaluation): Scientific

Notes: 80th Scientific Sessions of the American Heart Association, published in journal, Circulation 2007; 116:II-708.